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| Profile Name | BRAF V600E |
| Gene Variant Detail | |
| Relevant Treatment Approaches | BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor RAF Inhibitor (Pan) |
| Molecular Profile | Indication/Tumor Type | Response Type | Relevant Treatment Approaches | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|---|
| BRAF V600E | rectum cancer | sensitive | BRAF Inhibitor | Encorafenib + Panitumumab | Guideline | Actionable | Braftovi (encorafenib) in combination with Vectibix (panitumumab) is included in guidelines as primary or subsequent therapy for patients with rectal cancer harboring BRAF V600E (NCCN.org). | detail... |
| BRAF V600E | childhood pilocytic astrocytoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Selumetinib | Phase I | Actionable | In a Phase I trial, Koselugo (selumetinib) treatment resulted in a sustained partial response (PR) in 36% (9/25) and stable disease in 36% (9/25) of pediatric patients with pilocytic astrocytoma harboring KIAA1549-BRAF (n=18) or BRAF V600E (n=7), with a 2-year progression-free survival of 70%, and 29% (2/7) of the patients harboring BRAF V600E achieved PR (PMID: 31151904; NCT01089101). | 31151904 |
| BRAF V600E | melanoma | sensitive | Ulixertinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Ulixertinib (BVD-523) inhibited Erk signaling in melanoma cells harboring BRAF V600E, resulted in cell cycle arrest in culture and tumor growth inhibition in cell line xenograft models (PMID: 28939558). | 28939558 | |
| BRAF V600E | melanoma | decreased response | Nivolumab | Clinical Study - Cohort | Actionable | In a retrospective analysis, patients with melanoma harboring BRAF V600E (n=84) had decreased response rates (29% vs. 53%, p=0.059), progression-free survival (2.7 vs. 19 months, p=0.049), and overall survival (11.7 vs. 20.4 months, p=0.081) relative to patients with BRAF V600K (n=19) when treated with Keytruda (pembrolizumab) (n=62 and 17 for BRAF V600E and V600K, respectively) or Opdivo (nivolumab) (n=22 and 2 for BRAF V600E and V600K, respectively) (PMID: 30630828). | 30630828 | |
| BRAF V600E | thyroid gland Hurthle cell carcinoma | sensitive | RAF Inhibitor (Pan) | Vemurafenib | Guideline | Actionable | Zelboraf (vemurafenib) is included in guidelines for patients with recurrent, advanced, or metastatic thyroid Hurthle cell carcinoma harboring BRAF V600E for whom clinical trials are not available or appropriate (NCCN.org). | detail... |
| BRAF V600E | Advanced Solid Tumor | sensitive | RAF Inhibitor (Pan) | Vemurafenib | Phase II | Actionable | In a Phase II trial (MyPathway), Zelboraf (vemurafenib) treatment resulted in an objective response of 46% (12/26, 2 complete response, 10 partial response) in patients with advanced solid tumors harboring BRAF V600E, but only 4% (1/23, 1 partial response) in patients harboring non-V600 BRAF mutations (PMID: 29320312; NCT02091141). | 29320312 |
| BRAF V600E | Advanced Solid Tumor | sensitive | RAF Inhibitor (Pan) | Vemurafenib | Phase II | Actionable | In a Phase II trial (VE-BASKET), Zelboraf (vemurafenib) treatment resulted in an objective response rate of 33% (56/172) in patients with advanced solid tumors harboring BRAF V600E, including 5 patients with a complete response and 51 patients with a partial response, and led a duration of response of 13.1 months, a progression-free survival of 5.8 months, and an overall survival of 17.6 months (PMID: 32029534; NCT01524978). | 32029534 |
| BRAF V600E | cholangiocarcinoma | predicted - sensitive | BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, combination treatment with Tafinlar (dabrafenib) and Mekinist (trametinib) in a patient with metastatic cholangiocarcinoma harboring BRAF V600E who progressed on chemotherapy led to a sustained metabolic response for six months (PMID: 33537843). | 33537843 |
| BRAF V600E | lung non-small cell carcinoma | not predictive | Nivolumab | Clinical Study - Cohort | Actionable | In a retrospective analysis, non-small cell lung cancer patients harboring BRAF V600E did not demonstrate a significantly different response to treatment with either Keytruda (pembrolizumab), Opdivo (nivolumab), or Tecentriq (atezolizumab), compared to patients with BRAF non-V600E mutations, demonstrating an objective response rate of 25% (3/12) vs 33% (3/9) (p=1.0) and median progression-free survival of 3.7 months vs 4.1 months (p=0.37) (PMID: 29723688). | 29723688 | |
| BRAF V600E | neuroendocrine tumor | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor RAF Inhibitor (Pan) | Trametinib + Vemurafenib | Case Reports/Case Series | Actionable | In a clinical case study, Mekinist (trametinib) and Zelboraf (vemurafenib) combination treatment resulted in a rapid and sustained clinical response in a patient with a rectal neuroendocrine tumor harboring a BRAF V600E mutation (PMID: 27048246). | 27048246 |
| BRAF V600E | thyroid gland cancer | sensitive | BRAF Inhibitor | Dabrafenib + SCH772984 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, combination treatment with Tafinlar (dabrafenib) and SCH772984 synergistically inhibited cell growth of thyroid cancer cell lines harboring BRAF V600E in culture, and inhibited tumor growth in a cell line xenograft model (PMID: 33595872). | 33595872 |
| BRAF V600E | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib + TW-37 | Preclinical | Actionable | In a preclinical study, TW-37 enhanced the inhibitory effect of Mekinist (trametinib) on human melanoma cells harboring BRAF V600E in culture (PMID: 25665005). | 25665005 |
| BRAF V600E | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Cobimetinib | Phase I | Actionable | In a Phase I trial, Cotellic (cobimetinib) treatment resulted in a confirmed partial response in six melanoma patients harboring BRAF V600E (PMID: 27424159). | 27424159 |
| BRAF V600E | melanoma | sensitive | BRAF Inhibitor | BGB-283 | Preclinical - Cell culture | Actionable | In a preclinical study, BGB-283 inhibited Braf phosphorylation and cell proliferation in melanoma cell lines harboring BRAF V600E in culture (PMID: 26208524). | 26208524 |
| BRAF V600E | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Navitoclax + Trametinib | Preclinical | Actionable | In a preclinical study, Navitoclax (ABT-263) enhanced the inhibitory effect of Mekinist (trametinib) on human melanoma cells harboring BRAF V600E in culture (PMID: 25665005). | 25665005 |
| BRAF V600E | melanoma | resistant | RMC-4550 | Preclinical - Cell culture | Actionable | In a preclinical study, RMC-4550 did not inhibit Erk phosphorylation or proliferation of melanoma cells harboring BRAF V600E in culture (PMID: 30104724). | 30104724 | |
| BRAF V600E | melanoma | predicted - sensitive | BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Pembrolizumab + Trametinib | Phase II | Actionable | In a Phase II trial (IMPemBra), Keytruda (pembrolizumab) in combination with short-term or intermittent Tafinlar (dabrafenib) plus Mekinist (trametinib) resulted in improved median progression-free survival compared to Keytruda (pembrolizumab) monotherapy (27.0 vs 10.6 mo, p=0.13) in patients with treatment-naive advanced melanoma harboring BRAF V600E (n=26) or V600K (n=6) mutations (J Clin Oncol 38: 2020 (suppl; abstr 10021); NCT02625337). | detail... |
| BRAF V600E | colorectal cancer | sensitive | RAF Inhibitor (Pan) | INU-152 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, INU-152 inhibited growth of colorectal cancer cell lines harboring BRAF V600E in culture, and reduced tumor growth in BRAF V600E-mutant colorectal cancer cell line xenograft models (PMID: 28645859). | 28645859 |
| BRAF V600E | neuroendocrine tumor | predicted - sensitive | BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, Mekinist (trametinib) and Tafinlar (dabrafenib) combination treatment resulted in a rapid and sustained clinical response in a patient with a rectal neuroendocrine tumor harboring a BRAF V600E mutation (PMID: 27048246). | 27048246 |
| BRAF V600E | high grade glioma | predicted - sensitive | RAF Inhibitor (Pan) | Vemurafenib + ZM336372 | Preclinical - Patient cell culture | Actionable | In a preclinical study, combination treatment with Zelboraf (vemurafenib) and ZM336372 treatment led to inhibition of cell growth in a patient-derived glioma cell line harboring BRAF V600E in culture (PMID: 34433654). | 34433654 |
| BRAF V600E | thyroid gland follicular carcinoma | sensitive | RAF Inhibitor (Pan) | Vemurafenib | Guideline | Actionable | Zelboraf (vemurafenib) is included in guidelines for patients with recurrent, advanced, or metastatic thyroid follicular carcinoma harboring BRAF V600E for whom clinical trials are not available or appropriate (NCCN.org). | detail... |
| BRAF V600E | colorectal cancer | sensitive | BRAF Inhibitor | Regorafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Stivarga (regorafenib) inhibited proliferation of colorectal cancer cells harboring BRAF V600E in culture and suppressed angiogenesis and tumor growth in cell line xenograft models (PMID: 21170960). | 21170960 |
| BRAF V600E | colorectal cancer | decreased response | unspecified immune checkpoint inhibitor | Clinical Study - Cohort | Actionable | In a retrospective analysis, treatment with Keytruda (pembrolizumab), Opdivo (nivolumab), or combination treatment with Opdivo (nivolumab) and Yervoy (ipilimumab) in patients with mismatch repair-deficient colorectal cancer harboring BRAF V600E vs. patients with wild-type BRAF resulted in a lower objective response rate (44.4% vs. 74.2%, p = 0.12) and shorter progression-free survival (PFS) rates (1-year PFS 40% vs. 73.3%, 2-year PFS 26.7% vs. 73.3%) (PMID: 33631043). | 33631043 | |
| BRAF V600E | colorectal cancer | sensitive | RAF Inhibitor (Pan) | CCT241161 | Preclinical | Actionable | In a preclinical study, CCT241161 inhibited growth of colorectal cancer cell lines harboring BRAF V600E in culture (PMID: 25500121, PMID: 15294323). | 25500121 15294323 |
| BRAF V600E | colorectal cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical | Actionable | In a preclinical study, colorectal cancer cells harboring a BRAF V600E mutation had increased sensitivity to Mekinist (trametinib) compared to other colorectal cancer lines in culture (PMID: 25309914). | 25309914 |
| BRAF V600E | melanoma | sensitive | DEL-22379 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, DEL-22379 inhibited growth of melanoma cells harboring BRAF V600E with high levels of ERK dimerization in culture and inhibited tumor progression in melanoma xenograft models harboring BRAF V600E (PMID: 26267534). | 26267534 | |
| BRAF V600E | melanoma | no benefit | Palbociclib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, treatment with Ibrance (palbociclib) in a melanoma cell line xenograft model harboring BRAF V600E resulted in no benefit, demonstrating low but continuous growth (PMID: 27488531). | 27488531 | |
| BRAF V600E | melanoma | predicted - sensitive | JSI-1187 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, JSI-1187 treatment in a melanoma cell line harboring BRAF V600E led to inhibition of cell proliferation in culture, and tumor growth inhibition in a cell line xenograft model (Cancer Res 2020;80(16 Suppl):Abstract nr 4188). | detail... | |
| BRAF V600E | colorectal cancer | resistant | SHP099 | Preclinical - Cell culture | Actionable | In a preclincial study, colorectal cancer cell lines harboring BRAF V600E demonstrated resistance to SHP099 in culture (PMID: 27362227). | 27362227 | |
| BRAF V600E | colorectal cancer | sensitive | BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Pimasertib + Regorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Pimasertib (MSC1936369B) and Stivarga (regorafenib) synergistically inhibited proliferation of colorectal cancer cells harboring BRAF V600E in culture (PMID: 23629727). | 23629727 |
| BRAF V600E | melanoma | predicted - resistant | BI-3406 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, BI-3406 treatment failed to inhibit growth of KRAS wild-type melanoma cells harboring BRAF V600E in culture and in cell line xenograft models (PMID: 32816843). | 32816843 | |
| BRAF V600E | histiocytic sarcoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Case Reports/Case Series | Actionable | In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment resulted in an objective response rate of 37.9% (11/29) in patients with advanced solid tumors harboring BRAF V600E, 1 patient with histiocytic sarcoma of the brain achieved a partial response with an ongoing progression-free survival at 20.9 months (PMID: 32758030; NCT02465060). | 32758030 |
| BRAF V600E | melanoma | no benefit | RM-018 | Preclinical - Cell culture | Actionable | In a preclinical study, RM-018 did not inhibit growth of melanoma cells harboring BRAF V600E in culture (PMID: 33824136). | 33824136 | |
| BRAF V600E | melanoma | no benefit | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor RAF Inhibitor (Pan) | Cobimetinib + Pembrolizumab + Vemurafenib | Phase I | Actionable | In a Phase I trial, combination of Cotellic (cobimetinib), Zelboraf (vemurafenib), and Keytruda (pembrolizumab) resulted in unreached median progression-free survival and overall survival in patients with advanced melanoma harboring BRAF V600E or V600K mutations, however, the trial was closed due to high incidence of dose-limiting toxicity and decreased health utility at 1 year (J Clin Oncol 39, no. 15_suppl, abstract e21506; NCT02818023). | detail... |
| BRAF V600E | melanoma | no benefit | RAF Inhibitor (Pan) | Sorafenib | Phase II | Actionable | In a Phase II study, Nexavar (sorafenib) displayed negligible efficacy in melanoma patients with BRAF V600E mutations (PMID: 16880785, PMID: 22394203). | 22394203 16880785 |
| BRAF V600E | melanoma | sensitive | SBI-755199 | Preclinical | Actionable | In a preclinical study, SBI-755199 induced cell death in human melanoma cell lines harboring BRAF V600E in culture (PMID: 26603897). | 26603897 | |
| BRAF V600E | colon neuroendocrine neoplasm | no benefit | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib | Case Reports/Case Series | Actionable | In Phase II trial, Mektovi (binimetinib) therapy in a patient with recurrent neuroendocrine carcinoma of the colon harboring a BRAF V600E mutation who had previously progressed on Tafinlar (dabrafinib) resulted in disease progression after two cycles (PMID: 30181415; NCT01885195). | 30181415 |
| BRAF V600E | melanoma | decreased response | BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + SCH772984 + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, combination of Tafinlar (dabrafenib), SCH772984, and Mekinist (trametinib) resulted in durable inhibition of Erk signaling and proliferation of melanoma cells overexpressing BRAF V600E in culture (PMID: 28714990). | 28714990 |
| BRAF V600E | lung non-small cell carcinoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib + TW-37 | Preclinical | Actionable | In a preclinical study, TW-37 enhanced the inhibitory effect of Mekinist (trametinib) on human non-small cell lung cancer cells harboring BRAF V600E in culture (PMID: 25665005). | 25665005 |
| BRAF V600E | melanoma | sensitive | BRAF Inhibitor | EBI-907 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, EBI-907 inhibited BRAF and ERK signaling, resulted in growth inhibition of melanoma cells harboring BRAF V600E in culture and in cell line xenograft models (PMID: 26810733). | 26810733 |
| BRAF V600E | melanoma | sensitive | BRAF Inhibitor | Imatinib + PLX4720 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of Gleevec (imatinib) and PLX4720 enhanced antitumor efficacy of melanoma cells harboring BRAF V600E, demonstrating decreased cell survival in xenograft models, and decreased phosphorylation of Mapk1 in culture (PMID: 27924459). | 27924459 |
| BRAF V600E | thyroid gland cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dasatinib + Selumetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Sprycel (dasatinib) and Koselugo (selumetinib) synergistically inhibited proliferation and induced apoptosis in both parental thyroid cancer cell lines harboring BRAF V600E and those acquired Sprycel (dasatinib)-resistance in culture (PMID: 27222538). | 27222538 |
| BRAF V600E | Advanced Solid Tumor | no benefit | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Selumetinib | Clinical Study - Cohort | Actionable | In a Phase II trial (MATCH), Koselugo (selumetinib) treatment resulted in a 15% (3/20) six-month progression-free survival rate, no objective responses, and did not lead to tumor regression in pediatric patients with advanced solid tumors including high grade glioma (n=8) and rhabdomyosarcoma (n=7) that harbored MAPK pathway alterations including BRAF V600E, activating KRAS, HRAS, or NRAS mutations, or inactivating NF1 mutations (J Clin Oncol 39, no. 15_suppl (May 20, 2021) 10008; NCT03213691, NCT03155620). | detail... |
| BRAF V600E | melanoma | sensitive | BRAF Inhibitor | PLX4720 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, PLX4720 inhibited growth of melanoma cells harboring BRAF V600E in culture and in cell line xenograft models (PMID: 18287029). | 18287029 |
| BRAF V600E | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor RAF Inhibitor (Pan) | PAC-1 + Trametinib + Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, the addition of PAC-1 to Mekinist (trametinib) and Zelboraf (vemurafenib) led to greater levels of caspase-3 activity and apoptosis in melanoma cells harboring BRAF V600E when compared to Zelboraf (vemurafenib) and Mekinist (trametinib) treatment without PAC-1 (PMID: 27297867). | 27297867 |
| BRAF V600E | colorectal cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Pimasertib | Preclinical - Cell culture | Actionable | In a preclinical study, Pimasertib (MSC1936369B) inhibited proliferation of colorectal cancer cells harboring BRAF V600E in culture (PMID: 23629727). | 23629727 |
| BRAF V600E | melanoma | sensitive | RAF Inhibitor (Pan) | PAC-1 + Vemurafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of PAC-1 and Zelboraf (vemurafenib) resulted in a synergistic effect when treating melanoma cells harboring BRAF V600E in culture and xenograft models, demonstrating increased apoptosis and decreased tumor volume (PMID: 27297867). | 27297867 |
| BRAF V600E | melanoma | sensitive | RAF Inhibitor (Pan) | TAK-632 | Preclinical - Cell culture | Actionable | In a preclinical study, TAK-632 inhibited proliferation of melanoma cell lines harboring either monomeric BRAF V600E or dimeric isoform of V600E which conferred Zelboraf (vemurafenib)-resistance in culture (PMID: 27523909). | 27523909 |
| BRAF V600E | melanoma | sensitive | RAF Inhibitor (Pan) | TAK-632 | Preclinical - Cell culture | Actionable | In a preclinical study, TAK-632 treatment inhibited Erk phosphorylation and reduced proliferation of a melanoma cells harboring either monomeric BRAF V600E or dimeric isoform (p61) of V600E in culture (PMID: 30559419). | 30559419 |
| BRAF V600E | intrahepatic cholangiocarcinoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Case Reports/Case Series | Actionable | In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment resulted in an objective response rate of 37.9% (11/29) in patients with advanced solid tumors harboring BRAF V600E, of 4 patients with intrahepatic cholangiocarcinoma, 3 achieved a partial response, with individual progression-free survival of 12.8, 9.1, and 29.4 months (PMID: 32758030; NCT02465060). | 32758030 |
| BRAF V600E | pilocytic astrocytoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor RAF Inhibitor (Pan) | Cobimetinib + Vemurafenib | Guideline | Actionable | Zelboraf (vemurafenib) and Cotellic (cobimetinib) combination therapy is included in guidelines as an adjuvant treatment for patients with pilocytic astrocytoma harboring BRAF V600E (NCCN.org). | detail... |
| BRAF V600E | high grade glioma | no benefit | ZM336372 | Preclinical - Patient cell culture | Actionable | In a preclinical study, ZM336372 treatment did not lead to inhibition of cell growth in a patient-derived glioma cell line harboring BRAF V600E in culture (PMID: 34433654). | 34433654 | |
| BRAF V600E | thyroid gland cancer | predicted - sensitive | BRAF Inhibitor | BGB-283 | Case Reports/Case Series | Actionable | In a Phase I trial, Linfirafenib (BGB-283) treatment resulted in partial response in 15.1% (8/53) of solid tumor patients with BRAF mutations, including 2 thyroid cancer patients harboring BRAF V600E (1 in dose-escalation phase, 1 in the dose-expansion), and in the dose-expansion phase 1 of 3 thyroid cancer patients harboring a BRAF V600 mutation demonstrated a partial response and 2 demonstrated stable disease, resulting in a disease control rate of 100% (3/3) (PMID: 32182156; NCT02610361). | 32182156 |
| BRAF V600E | histiocytic and dendritic cell cancer | predicted - sensitive | RAF Inhibitor (Pan) | Vemurafenib | Case Reports/Case Series | Actionable | In a Phase II trial (VE-BASKET), responses were seen in patients with histiocytic neoplasms harboring BRAF V600E (n=27) when treated with Zelboraf (vemurafenib), including 15 patients with a partial response and 2 patients with a complete response (PMID: 32029534; NCT01524978). | 32029534 |
| BRAF V600E | skin melanoma | sensitive | BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib + Encorafenib | Guideline | Actionable | Braftovi (encorafenib) in combination with Mektovi (binimetinib) is included in guidelines as first-line and second-line therapy for patients with metastatic or unresectable cutaneous melanoma harboring BRAF V600E or V600K mutations (PMID: 30959471; NCCN.org). | detail... 30959471 |
| BRAF V600E | pilocytic astrocytoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Selumetinib | Guideline | Actionable | Koselugo (selumetinib) is included in guidelines for patients with recurrent or progressive pilocytic astrocytoma harboring BRAF V600E (NCCN.org). | detail... |
| BRAF V600E | lung non-small cell carcinoma | sensitive | RAF Inhibitor (Pan) | Navitoclax + Vemurafenib | Preclinical | Actionable | In a preclinical study, Navitoclax (ABT-263) enhanced the inhibitory effect of Zelboraf (vemurafenib) on human non-small cell lung cancer cells harboring BRAF V600E in culture (PMID: 25665005). | 25665005 |
| BRAF V600E | colorectal cancer | sensitive | ERAS-007 | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, ERAS-007 (ASN007) treatment inhibited cell proliferation and Erk signaling in colorectal cancer cell lines harboring BRAF V600E in culture, and induced tumor regression in two patient-derived xenograft (PDX) models (PMID: 34337566). | 34337566 | |
| BRAF V600E | melanoma | sensitive | BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Cediranib + PLX4720 + Selumetinib | Preclinical - Cell culture | Actionable | In a preclinical study, PLX4720, Cediranib (AZD-2171) and Koselugo (selumetinib) worked synergistically to inhibit cell growth in PLX4720-resistant melanoma cell lines harboring BRAF V600E in culture (PMID: 26461489). | 26461489 |
| BRAF V600E | melanoma | sensitive | RAF Inhibitor (Pan) | Vemurafenib | Phase I | Actionable | In a Phase I trial, Zelboraf (vemurafenib) treatment resulted in an overall response rate of 81% (26/32; 2 complete responses, 24 partial responses), and inhibition of tumor Erk and Ccnd1, and reduced cell proliferation in metastatic melanoma patients harboring BRAF V600E (PMID: 20818844; NCT00215605). | 20818844 |
| BRAF V600E | melanoma | sensitive | RAF Inhibitor (Pan) | Vemurafenib | FDA approved - On Companion Diagnostic | Actionable | In a Phase III trial (BRIM-3) that supported FDA approval, Zelboraf (vemurafenib), as compared to Deticene (dacarbazine), resulted in an improved overall survival (OS) (13.6 vs 9.7 months, HR=0.81, p=0.03) in patients with BRAF V600E-positive metastatic melanoma, with estimated OS rates of 56%, 30%, 21%, and 17% at 1, 2, 3, and 4 years, respectively (PMID: 28961848, PMID: 21639808; NCT01006980), and BRAF V600E is included on the companion diagnostic (FDA.gov). | 28961848 detail... detail... 21639808 |
| BRAF V600E | melanoma | sensitive | AZD0364 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, AZD0364 (ATG-017) inhibited cell growth, decreased phosphorylation of Erk target genes, and increased expression of apoptosis markers in melanoma cells harboring BRAF V600E in culture, and resulted in tumor regression in cell line xenograft models (PMID: 33273059). | 33273059 | |
| BRAF V600E | colon cancer | resistant | Cetuximab | Guideline | Actionable | Erbitux (cetuximab), as a monotherapy, is not indicated for use in colon cancer patients with BRAF V600E (NCCN.org). | detail... | |
| BRAF V600E | pleomorphic xanthoastrocytoma | predicted - sensitive | RAF Inhibitor (Pan) | Vemurafenib | Case Reports/Case Series | Actionable | In a Phase II trial (VE-BASKET), Zelboraf (vemurafenib) treatment resulted in an objective response rate of 42.9% (3/7, 1 complete response, 2 partial responses) and a clinical benefit rate of 57% in patients with pleomorphic xanthoastrocytoma harboring BRAF V600E, with a median progression-free survival of 5.7 months, and median overall survival not reached (PMID: 30351999; NCT01524978). | 30351999 |
| BRAF V600E | pleomorphic xanthoastrocytoma | predicted - sensitive | RAF Inhibitor (Pan) | Vemurafenib | Case Reports/Case Series | Actionable | In a clinical case study, Zelboraf (vemurafenib) treatment resulted in a complete intracranial response 2 months after treatment in a patient with anaplastic pleomorphic xanthoastrocytoma harboring BRAF V600E, although the disease progressed 1 month later (PMID: 31386052). | 31386052 |
| BRAF V600E | hairy cell leukemia | predicted - sensitive | RAF Inhibitor (Pan) | Ruxolitinib + Vemurafenib | Phase II | Actionable | In a Phase II trial (HCL-PG03), combined Zelboraf (vemurafenib) and Jakafi (ruxolitinib) therapy in relapsed or refractory hairy cell leukemia patients with BRAF V600E demonstrated safety, and led to complete response (CR) in 87% (26/30) of patients, including 17 (65%) with negative minimal residual disease, a progression-free survival rate of 78% at a median follow-up of 37 months, and a relapse-free survival rate of 85% in the 26 patients with a CR at a median follow-up of 34 months (PMID: 33979489). | 33979489 |
| BRAF V600E | colorectal cancer | sensitive | BRAF Inhibitor | Dabrafenib | Preclinical | Actionable | In a preclinical study, colorectal cancer cell lines harboring a BRAF V600E mutation had increased sensitivity to Tafinlar (dabrafenib) in culture compared to cell lines with wild-type BRAF (PMID: 24885690). | 24885690 |
| BRAF V600E | melanoma | predicted - sensitive | BRAF Inhibitor | RAF265 | Phase I | Actionable | In a Phase I trial, treatment with RAF265 in melanoma patients resulted in an objective response rate of 12.1% (8/66), including a partial response in four patients harboring BRAF V600E, two partial responses and one complete response in patients with wild-type BRAF, and one complete response in a patient with unknown mutational status (PMID: 28719152). | 28719152 |
| BRAF V600E | melanoma | sensitive | BRAF Inhibitor | Dabrafenib | FDA approved - On Companion Diagnostic | Actionable | In a Phase III clinical trial (BREAK-3) that supported FDA approval, Tafinlar (dabrafenib) improved median progression-free survival compared to Deticene (dacarbazine) (5.1 vs 2.7 months, HR=0.3, p<0.0001) in patients with BRAF V600E positive melanoma (PMID: 22735384; NCT01227889). | detail... detail... 22735384 |
| BRAF V600E | melanoma | sensitive | SBI-0640756 | Preclinical | Actionable | In a preclinical study, SBI-0640756 inhibited proliferation and Akt/mTOR signaling in human melanoma cell lines harboring BRAF V600E in culture (PMID: 26603897, PMID: 20531415). | 20531415 26603897 | |
| BRAF V600E | intrahepatic cholangiocarcinoma | predicted - sensitive | BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, combination treatment with Tafinlar (dabrafenib) and Mekinist (trametinib) in a patient with intrahepatic cholangiocarcinoma harboring BRAF V600E who progressed on chemotherapy led to stable disease at 6 weeks, improvement of lung and liver lesions at 12 weeks after treatment, and response was maintained until disease progression in the liver was observed at 10 months (PMID: 33537843). | 33537843 |
| BRAF V600E | brain glioblastoma multiforme | predicted - sensitive | BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, Tafinlar (dabrafenib) and Mekinist (trametinib) combination therapy resulted in tumor shrinkage after 2 months in a patient with epithelioid glioblastoma multiforme harboring BRAF V600E, who had progressed after resection, radiotherapy, and chemotherapy, and following an interruption in therapy due to toxicity demonstrated a partial response and remained progression-free for 19 months, prior to progressing 29 months after initiation of therapy (PMID: 33461766). | 33461766 |
| BRAF V600E | skin melanoma | sensitive | Ganetespib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the Hsp90 inhibitor Ganetespib destabilized BRAF, especially BRAF V600E, resulted in loss of cell viability in culture and antitumor effects in cell line xenograft models of melanoma (PMID: 24398428). | 24398428 | |
| BRAF V600E | colorectal adenocarcinoma | sensitive | ASTX029 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, ASTX029 treatment reduced Erk and Rsk phosphorylation and inhibited growth of colorectal adenocarcinoma cell lines harboring BRAF V600E in culture, and inhibited tumor growth and induced tumor regression in cell line xenograft models (PMID: 34330842). | 34330842 | |
| BRAF V600E | thyroid gland cancer | sensitive | RAF Inhibitor (Pan) | TAK-632 | Preclinical - Cell culture | Actionable | In a preclinical study, TAK-632 inhibited proliferation of thyroid cancer cells harboring BRAF V600E in culture (PMID: 27523909). | 27523909 |
| BRAF V600E | uveal melanoma | no benefit | YM-254890 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed mouse melanocytes expressing BRAF V600E were insensitive to treatment with YM-254890 (PMID: 33229459). | 33229459 | |
| BRAF V600E | colorectal cancer | sensitive | BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, combination therapy consisting of Tafinlar (dabrafenib) and Mekinist (trametinib) inhibited survival of colorectal cancer cell lines harboring BRAF V600E in culture (PMID: 27312529). | 27312529 |
| BRAF V600E | Advanced Solid Tumor | predicted - sensitive | PF-00477736 + PF3644022 | Preclinical - Cell culture | Actionable | In a preclinical study, Chk1 inhibitor PF-477736 and MK2 inhibitor PF3644022 synergistically inhibited growth of transformed cells over expressing BRAF V600E in culture, while single agent inhibition had no effect (PMID: 26140595). | 26140595 | |
| BRAF V600E | pancreatic ductal adenocarcinoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Cobimetinib + Gemcitabine + Nab-paclitaxel | Case Reports/Case Series | Actionable | In a clinical case study, Gemzar (gemcitabine), Abraxane (nab-paclitaxel), and Cotellic (cobimetinib) combination treatment resulted in a complete radiologic response within 6 months of initiation lasting at least 16 months in a patient with microsatellite stable, KRAS wild-type pancreatic ductal adenocarcinoma harboring BRAF V600E (PMID: 34667063). | 34667063 |
| BRAF V600E | colon adenocarcinoma | not applicable | N/A | Phase III | Emerging | In a post-hoc analysis of a Phase III trial, BRAF V600E mutations in colon adenocarcinoma patients with microsatellite stable tumors were associated with a shorter disease-free survival and overall survival compared to those patients with microsatellite instability tumors, suggesting that BRAF V600E may serve as a future prognostic biomarker in this patient population (PMID: 26768652). | 26768652 | |
| BRAF V600E | thyroid gland anaplastic carcinoma | sensitive | BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Clinical Study | Actionable | In a clinical case report, Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment resulted in a clinical and radiologic response that lasted for 9 months in an anaplastic thyroid cancer patient harboring BRAF V600E (PMID: 27697975). | 27697975 |
| BRAF V600E | thyroid gland anaplastic carcinoma | sensitive | BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | FDA approved - On Companion Diagnostic | Actionable | In a Phase II trial (ROAR) that supported FDA approval, the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in an overall response rate of 69% (11/16; 1 complete response and 10 partial responses) in patients with anaplastic thyroid cancer harboring BRAF V600E (PMID: 29072975; NCT02034110). | 29072975 detail... detail... |
| BRAF V600E | thyroid gland anaplastic carcinoma | sensitive | BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Guideline | Actionable | Tafinlar (dabrafenib) and Mekinist (trametinib) combination therapy is included in guidelines for metastatic thyroid gland anaplastic carcinoma patients harboring BRAF V600E (NCCN.org). | detail... |
| BRAF V600E | melanoma | sensitive | MEK1 Inhibitor | E6201 | Preclinical | Actionable | In a preclinical study, E6201 inhibited Mapk pathway activation and proliferation of melanoma cell lines harboring BRAF V600E mutation in culture (PMID: 24448821). | 24448821 |
| BRAF V600E | melanoma | sensitive | MEK1 Inhibitor | E6201 | Case Reports/Case Series | Actionable | In a Phase I trial, a patient with metastatic melanoma and brain metastasis harboring BRAF V600E demonstrated an ongoing near complete response with an overall survival of more than 8 years, and preclinical analysis of melanoma cell lines harboring homozygous or heterozygous BRAF V600E in culture were sensitive to treatment with E6201 (PMID: 30264293). | 30264293 |
| BRAF V600E | pilocytic astrocytoma | predicted - sensitive | BRAF Inhibitor | Dabrafenib | Case Reports/Case Series | Actionable | In a clinical case study, Tafinlar (dabrafenib) treatment resulted in a near complete response and resolution of leptomeningeal dissemination in a patient with pilocytic astrocytoma harboring BRAF V600E (PMID: 28784858). | 28784858 |
| BRAF V600E | low grade glioma | sensitive | BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Phase II | Actionable | In a Phase II trial (ROAR), Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment resulted in an objective response rate of 69% (9/13, 1 complete response, 6 partial responses, 2 minor responses) in patients with low-grade glioma harboring BRAF V600E, with median duration of response, median progression-free survival, and overall survival time unreached (PMID: 34838156; NCT02034110). | 34838156 |
| BRAF V600E | low grade glioma | sensitive | BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Guideline | Actionable | Combination of Mekinist (trametinib) and Tafinlar (dabrafenib) is included in guidelines for patients with recurrent or progressive low grade glioma harboring BRAF V600E (NCCN.org). | detail... |
| BRAF V600E | melanoma | sensitive | RAF Inhibitor (Pan) | CCT196969 | Preclinical - Pdx | Actionable | In a preclinical study, CCT196969 inhibited growth of a human melanoma cell line harboring BRAF V600E in culture, and induced tumor regression in several BRAF V600E-mutant melanoma patient-derived xenograft models (PMID: 25500121). | 25500121 |
| BRAF V600E | lung non-small cell carcinoma | sensitive | RAF Inhibitor (Pan) | Vemurafenib | Guideline | Actionable | Zelboraf (vemurafenib) is in guidelines for metastatic non-small cell lung cancer patients with BRAF V600E mutations who can not tolerate the combination of Mekinist (trametinib) and Tafinlar (dabrafenib) (NCCN.org). | detail... |
| BRAF V600E | lung non-small cell carcinoma | sensitive | RAF Inhibitor (Pan) | Vemurafenib | Phase II | Actionable | In a Phase II trial (MyPathway), Zelboraf (vemurafenib) treatment resulted in an objective response of 43% (6/14, 1 complete response, 5 partial response) in patients with non-small cell lung cancer harboring BRAF V600E, and stable disease lasting more than 120 days in 2 patients (PMID: 29320312; NCT02091141). | 29320312 |
| BRAF V600E | lung non-small cell carcinoma | sensitive | RAF Inhibitor (Pan) | Vemurafenib | Case Reports/Case Series | Actionable | In a clinical case study, a non-small cell lung cancer patient harboring a BRAF V600E mutation had a complete response after treatment with Zelboraf (vemurafenib) (PMID: 23733758). | 23733758 |
| BRAF V600E | lung non-small cell carcinoma | sensitive | RAF Inhibitor (Pan) | Vemurafenib | Phase II | Actionable | In a Phase II trial (VE-BASKET), responses were seen in patients with non-small cell lung cancer harboring BRAF V600E (n=63) when treated with Zelboraf (vemurafenib), including 23 patients with a partial response (PMID: 32029534; NCT01524978). | 32029534 |
| BRAF V600E | lung non-small cell carcinoma | sensitive | RAF Inhibitor (Pan) | Vemurafenib | Clinical Study | Actionable | In a retrospective analysis, non-small cell lung cancer patients harboring BRAF V600E achieved an overall response rate of 54% (13/24, 2 complete responses, 11 partial responses, and 10 with stable disease) and a disease control rate of 96% following treatment with Zelboraf (vemurafenib) (PMID: 26200454). | 26200454 |
| BRAF V600E | colorectal cancer | predicted - sensitive | LY3214996 | Preclinical - Cell culture | Actionable | In a preclinical study, a lung cancer cell line harboring BRAF V600E and NF1 T2805I was sensitive to treatment with LY3214996 in culture, demonstrating decreased cell viability (PMID: 31744895). | 31744895 | |
| BRAF V600E | ovarian serous carcinoma | predicted - sensitive | BRAF Inhibitor | BGB-283 | Case Reports/Case Series | Actionable | In a Phase I trial, Lifirafenib (BGB-283) treatment demonstrated safety and resulted in partial response (PR) in 15.1% (8/53) of advanced solid tumor patients harboring a BRAF mutation, including 1 patient with BRAF V600E-mutant low-grade serous ovarian cancer (PMID: 32182156; NCT02610361). | 32182156 |
| BRAF V600E | high grade glioma | predicted - sensitive | BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | PLX4720 + Selumetinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Selumetinib (AZD6244) and PLX4720 synergistically inhibited growth and induced apoptosis in glioma cell lines in culture, resulted in prolonged survival in cell line xenograft models (PMID: 27217440). | 27217440 |
| BRAF V600E | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | GSK2126458 + Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) in combination with Omipalisib (GSK2126458) inhibited growth of melanoma cell lines harboring BRAF V600E in culture (PMID: 22389471). | 22389471 |
| BRAF V600E | melanoma | sensitive | BRAF Inhibitor | Dabrafenib + GSK2126458 | Preclinical | Actionable | In a preclinical study, Tafinlar (dabrafenib) in combination with Omipalisib (GSK2126458) resulted in improved growth inhibition of human melanoma cell lines harboring BRAF V600E in culture (PMID: 22389471). | 22389471 |
| BRAF V600E | Advanced Solid Tumor | sensitive | BRAF Inhibitor | PLX8394 | Preclinical | Actionable | In a preclinical study, PLX8394 had been shown to block survival and growth of vemurafenib/PLX4720-resistant cells harboring distinct BRAF V600E splice variants (PMID: 24422853). | 24422853 |
| BRAF V600E | Erdheim-Chester disease | sensitive | BRAF Inhibitor | Dabrafenib | Guideline | Actionable | Tafinlar (dabrafenib) is included in guidelines as first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring BRAF V600E (NCCN Guidelines). | detail... |
| BRAF V600E | colorectal cancer | sensitive | BRAF Inhibitor | BGB-283 + Cetuximab | Preclinical - Cell line xenograft | Actionable | In a preclinical study, BGB-283 in combination with Erbitux (cetuximab) demonstrated enhanced tumor suppression in colorectal cancer cell line xenograft models harboring BRAF V600E (PMID: 26208524). | 26208524 |
| BRAF V600E | melanoma | sensitive | BRAF Inhibitor | ASN003 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, a melanoma xenograft model harboring BRAF V600E demonstrated tumor regression when treated with ASN003 (Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr B100). | detail... |
| BRAF V600E | renal cell carcinoma | predicted - sensitive | RAF Inhibitor (Pan) | Vemurafenib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with metastatic renal cell carcinoma harboring BRAF V600E demonstrated a partial response following treatment with Zelboraf (vemurafenib) (PMID: 26918217). | 26918217 |
| BRAF V600E | pancreatic acinar cell adenocarcinoma | predicted - sensitive | BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, combination treatment with Tafinlar (dabrafenib) and Mekinist (trametinib) in a patient with pancreatic acinar cell carcinoma harboring BRAF V600E who had previously progressed on chemotherapy led to a response at 8 weeks, and ongoing clinical and radiological response was still observed at 32 months of treatment (PMID: 33537843). | 33537843 |
| BRAF V600E | diffuse large B-cell lymphoma | sensitive | ERAS-007 | Preclinical - Cell culture | Actionable | In a preclinical study, ERAS-007 (ASN007) treatment inhibited proliferation of diffuse large B-cell lymphoma cells harboring BRAF V600E in culture (PMID: 34337566). | 34337566 | |
| BRAF V600E | colorectal cancer | sensitive | RAF Inhibitor (Pan) | Capecitabine + Vemurafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Zelboraf (vemurafenib) treatment in combination with Xeloda (capecitabine) enhanced tumor growth inhibition and increased survival in a cell line xenograft model of colorectal cancer harboring BRAF V600E (PMID: 22180495). | 22180495 |
| BRAF V600E | colon cancer | sensitive | BRAF Inhibitor | PLX4720 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, PLX4720 inhibited growth of colon cancer cells harboring BRAF V600E in culture and in cell line xenograft models (PMID: 18287029). | 18287029 |
| BRAF V600E | high grade glioma | sensitive | BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Phase II | Actionable | In a Phase II trial (ROAR), Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment resulted in an objective response rate of 33% (15/45, 3 complete responses, 12 partial responses) in patients with high-grade glioma harboring BRAF V600E, with a median duration of response of 36.9 months, a median progression-free survival of 3.8 months, and an overall survival of 17.6 months (PMID: 34838156; NCT02034110). | 34838156 |
| BRAF V600E | colon adenocarcinoma | predicted - sensitive | BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Regorafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, combination treatment with Stivarga (regorafenib), Tafinlar (dabrafenib), and Mekinist (trametinib) in a patient with colon adenocarcinoma harboring BRAF V600E led to stable disease, and treatment continued for eight months, at which time some disease progression was observed (PMID: 33568355). | 33568355 |
| BRAF V600E | high grade glioma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Everolimus + Selumetinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Selumetinib (AZD6244) and Afinitor (everolimus) synergistically inhibited growth and induced apoptosis in glioma cell lines in culture, resulted in prolonged survival in cell line xenograft models (PMID: 27217440). | 27217440 |
| BRAF V600E | melanoma | predicted - resistant | KRT-232 | Preclinical - Pdx | Actionable | In a preclinical study, patient-derived xenograft (PDX) models of melanoma harboring BRAF V600E demonstrated resistance to treatment with KRT-232 (AMG 232) (PMID: 32234759). | 32234759 | |
| BRAF V600E | colorectal cancer | sensitive | BRAF Inhibitor | Cetuximab + Dabrafenib + SCH772984 | Preclinical - Cell culture | Actionable | In a preclinical study, combination therapy consisting of Erbitux (cetuximab), Tafinlar (dabrafenib), and SCH772984 inhibited survival of colorectal cancer cell lines harboring BRAF V600E in culture (PMID: 27312529). | 27312529 |
| BRAF V600E | anaplastic oligodendroglioma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor RAF Inhibitor (Pan) | Cobimetinib + Vemurafenib | Guideline | Actionable | Combination of Zelboraf (vemurafenib) and Cotellic (cobimetinib) is included in guidelines for patients with recurrent anaplastic gliomas harboring BRAF V600E, including anaplastic oligodendroglioma (NCCN.org). | detail... |
| BRAF V600E | colorectal cancer | sensitive | BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Regorafenib + Trametinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, combination treatment with Stivarga (regorafenib), Tafinlar (dabrafenib), and Mekinist (trametinib) in colorectal cancer cell lines harboring BRAF V600E resulted in suppression of colony formation in culture, and inhibition of tumor growth in a cell line xenograft model (PMID: 33568355). | 33568355 |
| BRAF V600E | salivary gland carcinoma | predicted - sensitive | RAF Inhibitor (Pan) | Vemurafenib | Case Reports/Case Series | Actionable | In a Phase II (MyPathway) trial, Zelboraf (vemurafenib) treatment resulted in a partial response in a patient with advanced salivary gland carcinoma harboring BRAF V600E, with a progression-free survival of 18.5 months (PMID: 32067683; NCT02091141). | 32067683 |
| BRAF V600E | colorectal cancer | sensitive | RAF Inhibitor (Pan) | Panitumumab + Vemurafenib | Phase I | Actionable | In a Phase I trial, 83% (10/12) of patients with colorectal cancer carrying a BRAF V600E mutation demonstrated tumor regression when treated with a combination of Zelboraf (vemurafenib) and Vectibix (panitumumab) (PMID: 25589621). | 25589621 |
| BRAF V600E | colorectal cancer | sensitive | BRAF Inhibitor | Afatinib + BI 882370 | Preclinical | Actionable | In a preclinical study, colorectal cancer cells harboring BRAF V600E were sensitive to the combination of BI 882370 and Gilotrif (afatinib) in xenograft models, resulting in tumor growth inhibition and partial tumor regression (PMID: 26916115). | 26916115 |
| BRAF V600E | skin melanoma | sensitive | BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Guideline | Actionable | Tafinlar (dabrafenib) and Mekinist (trametinib) combination therapy is included in guidelines for cutaneous melanoma patients harboring a BRAF V600 activating mutation, such as BRAF V600E, as adjuvant therapy for stage III disease and as systemic therapy for patients with unresectable or metastatic disease (NCCN.org). | detail... |
| BRAF V600E | colorectal cancer | sensitive | BRAF Inhibitor | EBI-907 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, EBI-907 inhibited BRAF and ERK signaling, resulted in growth inhibition of colorectal cancer cells harboring BRAF V600E in culture and in cell line xenograft models (PMID: 26810733). | 26810733 |
| BRAF V600E | pleomorphic xanthoastrocytoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Case Reports/Case Series | Actionable | In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment resulted in an objective response rate of 37.9% (11/29) in patients with advanced solid tumors harboring BRAF V600E, 1 patient with pleomorphic xanthoastrocytoma achieved a partial response lasting 7.2 months (PMID: 32758030; NCT02465060). | 32758030 |
| BRAF V600E | melanoma | sensitive | BRAF Inhibitor | Navitoclax + PLX4720 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, PLX4720 and navitoclax (ABT-263) worked synergistically to inhibit growth and increase apoptosis of BRAF V600E mutant melanoma cells in culture and in xenografts (PMID: 24983357). | 24983357 |
| BRAF V600E | colorectal cancer | predicted - sensitive | Ravoxertinib | Case Reports/Case Series | Actionable | In a Phase I trial, two colorectal cancer patients harboring BRAF V600E achieved partial responses lasting 21 and 73 weeks following treatment with Ravoxertinib (GDC-0994) (PMID: 31848189; NCT01875705). | 31848189 | |
| BRAF V600E | glioblastoma | decreased response | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | PD-0325901 | Preclinical - Cell culture | Actionable | In a preclinical study, a glioblastoma cell line harboring BRAF V600E demonstrated a decreased response to treatment with PD-0325901, demonstrating increased viability of CD133 positive cells in culture (PMID: 26573800). | 26573800 |
| BRAF V600E | melanoma | sensitive | BRAF Inhibitor | PLX4720 + Vorinostat | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of PLX4720 and Zolinza (vorinostat) resulted in antitumor efficacy in a melanoma cell line harboring BRAF V600E, demonstrating decreased cell survival and increased apoptotic activity in xenograft models, and decreased Rb phosphorylation in culture (PMID: 27924459). | 27924459 |
| BRAF V600E | melanoma | sensitive | DETD-35 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, DETD-35 inhibited proliferation and colony formation of melanoma cells harboring BRAF V600E in culture and reduced tumor size in xenograft models (PMID: 27048951). | 27048951 | |
| BRAF V600E | lymphatic system cancer | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Cobimetinib | Case Reports/Case Series | Actionable | In a Phase II trial, treatment with Cotellic (cobimetinib) in patients with histiocytic neoplasms resulted in a PET overall response rate of 89% (16/18), with complete response in 72% (13/18) and partial response in 17% (3/18), and resulted in stable disease in 6% (1/18) of patients, including 1 partial response and 3 complete responses in 4 patients with Erdheim-Chester disease harboring BRAF V600E (PMID: 30867592; NCT01953926). | 30867592 |
| BRAF V600E | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | BI-847325 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, treatment with BI-847325 resulted in decreased expression of Mcl-1 and Mek, and inhibited growth of melanoma cell lines harboring BRAF V600E in culture, and inhibited tumor growth in xenograft models of BRAF V600E-positive melanoma, including models with BRAF-inhibitor resistance (PMID: 25873592). | 25873592 |
| BRAF V600E | ganglioglioma | predicted - sensitive | BRAF Inhibitor | Dabrafenib | Case Reports/Case Series | Actionable | In a clinical case study, Tafinlar (dabrafenib) treatment resulted in partial response 8 weeks after therapy initiation in a pediatric patient with anaplastic ganglioglioma harboring BRAF V600E, but disease progression occurred at 40 weeks due to acquired resistance (PMID: 29880583). | 29880583 |
| BRAF V600E | colon cancer | resistant | Panitumumab | Guideline | Actionable | Vectibix (panitumumab), as a monotherapy, is not indicated for use in colon cancer patients with BRAF V600E (NCCN.org). | detail... | |
| BRAF V600E | melanoma | sensitive | SBI-0640726 | Preclinical | Actionable | In a preclinical study, SBI-0640726 inhibited proliferation and Akt/mTOR signaling in human melanoma cell lines harboring BRAF V600E in culture (PMID: 26603897, PMID: 20531415). | 20531415 26603897 | |
| BRAF V600E | thyroid gland anaplastic carcinoma | predicted - sensitive | RAF Inhibitor (Pan) | Vemurafenib | Case Reports/Case Series | Actionable | In a Phase II trial (VE-BASKET), Zelboraf (vemurafenib) treatment resulted in a response in patients with anaplastic thyroid carcinoma harboring BRAF V600E (n=12), including 1 patient with a complete response and 2 patients with a partial response (PMID: 32029534; NCT01524978). | 32029534 |
| BRAF V600E | melanoma | sensitive | RAF Inhibitor (Pan) | SBI-0640756 + Vemurafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Zelboraf (vemurafenib) in combination with SBI-0640756 inhibited the association of eIF4G1 and eIF4E in Zelboraf (vemurafenib) resistant human melanoma cell lines harboring BRAF V600E in culture and reduced tumor growth in xenograft models (PMID: 26603897). | 26603897 |
| BRAF V600E | melanoma | sensitive | BRAF Inhibitor | Cediranib + PLX4720 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, PLX4720 and Cediranib (AZD-2171) worked synergistically to inhibit cell growth and induce apoptosis in PLX4720-resistant human melanoma cell lines harboring BRAF V600E in culture and to suppress tumor growth in xenograft models (PMID: 26461489). | 26461489 |
| BRAF V600E | pilocytic astrocytoma | sensitive | BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Guideline | Actionable | Combination of Mekinist (trametinib) and Tafinlar (dabrafenib) is included in guidelines as an adjuvant treatment for patients with pilocytic astrocytoma harboring BRAF V600E (NCCN.org). | detail... |
| BRAF V600E | basal cell carcinoma | predicted - sensitive | BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in stable disease after three months of treatment in a patient with basal cell carcinoma harboring BRAF V600E (PMID: 33537843) | 33537843 |
| BRAF V600E | colorectal cancer | sensitive | Cetuximab + SCH772984 | Preclinical - Cell culture | Actionable | In a preclinical study, combination therapy consisting of Erbitux (cetuximab) and SCH772984 inhibited survival of colorectal cancer cell lines harboring BRAF V600E in culture (PMID: 27312529). | 27312529 | |
| BRAF V600E | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Selumetinib | Phase II | Actionable | In a Phase II trial, a favorable response rate to selumetinib (AZD6244) was observed in mutant BRAF but not BRAF wild-type melanoma patients (PMID: 22048237). | 22048237 |
| BRAF V600E | melanoma | sensitive | BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Phase II | Actionable | In a Phase II trial, BRAF V600E positive melanoma patients who progressed on treatment with BRAF inhibitors or the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) were treated again with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) after 12 weeks off treatment, which resulted in a partial response in 35% (8/25) and stable disease in 40% (10/25) (PMID: 28268064). | 28268064 |
| BRAF V600E | melanoma | sensitive | BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | FDA approved - On Companion Diagnostic | Actionable | In a Phase III trial (COMBI-v) that supported FDA approval, the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in an improved overall survival rate at 12 months (72% vs 65%, HR=0.69, p=0.005), median progression-free survival (11.4 vs 7.3 months, HR=0.56, p<0.001), and objective response rate (64% vs 51%, p<0.001) compared to Zelboraf (vemurafenib) in melanoma patients harboring BRAF V600E or V600K (PMID: 25399551; NCT01597908). | detail... detail... 25399551 |
| BRAF V600E | melanoma | sensitive | BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Preclinical | Actionable | In a preclinical study, Tafinlar (dabrafenib) in combination with Mekinist (trametinib) inhibited growth of melanoma cells harboring BRAF V600E in culture (PMID: 22389471). | 22389471 |
| BRAF V600E | colorectal cancer | sensitive | Ulixertinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Ulixertinib (BVD-523) inhibited Erk signaling in colorectal cancer cells harboring BRAF V600E, resulted in cell cycle arrest in culture and tumor growth inhibition in cell line xenograft models (PMID: 28939558). | 28939558 | |
| BRAF V600E | melanoma | sensitive | LY3214996 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, LY3214996 treatment in a melanoma cell line harboring BRAF V600E led to decreased cell proliferation in culture, and inhibition of tumor growth in a cell line xenograft model (PMID: 31744895). | 31744895 | |
| BRAF V600E | colorectal cancer | sensitive | BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + RAF709 + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, combination treatment with RAF709, Tafinlar (dabrafenib), and Mekinist (trametinib) in colorectal cancer cell lines harboring BRAF V600E resulted in suppression of colony formation in culture (PMID: 33568355). | 33568355 |
| BRAF V600E | colorectal cancer | sensitive | RAF Inhibitor (Pan) | TAK-632 | Preclinical - Cell culture | Actionable | In a preclinical study, TAK-632 inhibited proliferation of colorectal cancer cells harboring BRAF V600E in culture (PMID: 27523909). | 27523909 |
| BRAF V600E | skin melanoma | sensitive | BRAF Inhibitor | Dabrafenib | Guideline | Actionable | Tafinlar (dabrafenib) therapy is included in guidelines for cutaneous melanoma patients with unresectable or metastatic disease harboring BRAF V600 activating mutations, such as BRAF V600E, in cases where BRAF/MEK inhibitor combination therapy is contraindicated (NCCN.org). | detail... |
| BRAF V600E | skin melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor RAF Inhibitor (Pan) | Cobimetinib + Vemurafenib | Guideline | Actionable | Zelboraf (vemurafenib) and Cotellic (cobimetinib) combination therapy is included in cutaneous melanoma guidelines for patients with metastatic or unresectable disease harboring a BRAF V600 activating mutation (NCCN.org). | detail... |
| BRAF V600E | lung non-small cell carcinoma | not predictive | Atezolizumab | Clinical Study - Cohort | Actionable | In a retrospective analysis, non-small cell lung cancer patients harboring BRAF V600E did not demonstrate a significantly different response to treatment with either Keytruda (pembrolizumab), Opdivo (nivolumab), or Tecentriq (atezolizumab) compared to patients with BRAF non-V600E mutations, demonstrating an objective response rate of 25% (3/12) vs 33% (3/9) (p=1.0) and median progression-free survival of 3.7 months vs 4.1 months (p=0.37) (PMID: 29723688). | 29723688 | |
| BRAF V600E | melanoma | sensitive | Dasatinib | Preclinical | Actionable | In a preclinical study, Sprycel (dasatinib) inhibited cell invasion, cell signaling, and proliferation in human melanoma cell lines harboring BRAF V600E that are resistant to Braf inhibition in culture and in animal models (PMID: 23242808). | 23242808 | |
| BRAF V600E | colorectal cancer | predicted - sensitive | JSI-1187 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, JSI-1187 treatment in a colorectal cancer cell line harboring BRAF V600E led to inhibition of cell proliferation in culture, and tumor regression and dose-dependent tumor growth inhibition in a cell line xenograft model (Cancer Res 2020;80(16 Suppl):Abstract nr 4188). | detail... | |
| BRAF V600E | thyroid gland cancer | conflicting | RAF Inhibitor (Pan) | Vemurafenib | Case Reports/Case Series | Actionable | In a Phase II trial (MyPathway), Zelboraf (vemurafenib) treatment resulted in complete response in a patient with anaplastic thyroid cancer harboring BRAF V600E (PMID: 29320312; NCT02091141). | 29320312 |
| BRAF V600E | thyroid gland cancer | conflicting | RAF Inhibitor (Pan) | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, thyroid cancer cells harboring BRAF V600E demonstrated decreased sensitivity to Zelboraf (vemurafenib) in culture (PMID: 27523909). | 27523909 |
| BRAF V600E | endometrial adenocarcinoma | predicted - sensitive | BRAF Inhibitor | Dabrafenib + Rabeprazole + Rifampin | Case Reports/Case Series | Actionable | In a Phase I trial, combination treatment with Tafinlar (dabrafenib), Rabeprazol, and Rifampin in a patient with metastatic endometrial adenocarcinoma harboring BRAF V600E, that recurred 11 years after original diagnosis and was refractory to treatment with chemotherapy, led to reduction of lung metastases and pelvic tissue mass at three months, but a slight increase in pelvic mass was observed at six months (PMID: 33537843; NCT01954043). | 33537843 |
| BRAF V600E | pleomorphic xanthoastrocytoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor RAF Inhibitor (Pan) | Cobimetinib + Vemurafenib | Guideline | Actionable | Zelboraf (vemurafenib) and Cotellic (cobimetinib) combination therapy is included in guidelines as an adjuvant treatment for patients with pleomorphic xanthoastrocytoma harboring BRAF V600E (NCCN.org). | detail... |
| BRAF V600E | cholangiocarcinoma | predicted - sensitive | RAF Inhibitor (Pan) | Vemurafenib | Case Reports/Case Series | Actionable | In a Phase II trial (VE-BASKET), responses were seen in patients with cholangiocarcinoma harboring BRAF V600E (n=9) when treated with Zelboraf (vemurafenib), including 2 patients with a partial response (PMID: 32029534; NCT01524978). | 32029534 |
| BRAF V600E | hairy cell leukemia | not applicable | N/A | Guideline | Diagnostic | BRAF V600E is diagnostic and aids in distinguishing classic hairy cell leukemia (cHCL) from variant hairy cell leukemia (HCLv) and other B-cell lymphomas and leukemias (PMID: 29118233, NCCN.org). | detail... 29118233 | |
| BRAF V600E | glioblastoma | predicted - sensitive | BRAF Inhibitor | Dabrafenib | Case Reports/Case Series | Actionable | In a clinical case study, a previously treated pediatric patient with epithelioid glioblastoma harboring BRAF V600E demonstrated stable disease for 10 months when treated with Tafinlar (dabrafenib) (PMID: 29621181). | 29621181 |
| BRAF V600E | colorectal cancer | sensitive | RAF Inhibitor (Pan) | Cetuximab + Irinotecan + Vemurafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Zelboraf (vemurafenib) treatment in combination with Erbitux (cetuximab) and Camptosar (irinotecan) enhanced tumor growth inhibition and increased survival in a cell line xenograft model of colorectal cancer harboring BRAF V600E (PMID: 22180495). | 22180495 |
| BRAF V600E | colorectal cancer | sensitive | RAF Inhibitor (Pan) | Cetuximab + Irinotecan + Vemurafenib | Phase II | Actionable | In a Phase II trial (SWOG1406), addition of Zelboraf (vemurafenib) to Camptosar (irinotecan) plus Erbitux (cetuximab) improved progression-free survival (4.4 vs. 2.0 mo, HR 0.50, p=0.001), response rate (17% vs 4%, p=0.05), and disease control rate (67% vs. 22%, p<0.001) in patients with metastatic colorectal cancer harboring BRAF V600E (PMID: 33356422; NCT02164916). | 33356422 |
| BRAF V600E | salivary gland cancer | predicted - sensitive | RAF Inhibitor (Pan) | Vemurafenib | Case Reports/Case Series | Actionable | In a Phase II trial (VE-BASKET), a patient with salivary ductal carcinoma harboring BRAF V600E demonstrated a partial response when treated with Zelboraf (vemurafenib) (PMID: 32029534; NCT01524978). | 32029534 |
| BRAF V600E | colorectal cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Everolimus + Pimasertib | Preclinical - Cell culture | Actionable | In a preclinical study, Pimasertib (MSC1936369B) and Afinitor (everolimus) synergistically inhibited proliferation of colorectal cancer cells harboring BRAF V600E in culture (PMID: 23629727). | 23629727 |
| BRAF V600E | thyroid gland cancer | sensitive | RAF Inhibitor (Pan) | Ponatinib + Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Iclusig (ponatinib) and Zelboraf (vemurafenib) treatment synergistically inhibited proliferation of thyroid cancer cells harboring BRAF V600E in culture (PMID: 31937621). | 31937621 |
| BRAF V600E | ovarian cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | CI-1040 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, CI-1040 inhibited growth of a human ovarian cancer cell line harboring BRAF V600E in culture, and inhibited tumor growth in xenograft models (PMID: 19018267). | 19018267 |
| BRAF V600E | colorectal cancer | sensitive | BRAF Inhibitor RAF Inhibitor (Pan) | PLX4720 + TAK-632 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, PLX4720 and TAK-632 combination treatment resulted in durable inhibition of Erk signaling and tumor growth in xenograft models of colorectal cancer cells harboring BRAF V600E (PMID: 27523909). | 27523909 |
| BRAF V600E | lung non-small cell carcinoma | sensitive | BRAF Inhibitor | Dabrafenib | Phase II | Actionable | In a Phase II trial, 33% (26/78) of previously treated non-small cell lung carcinoma patients harboring BRAF V600E demonstrated an overall response, which included all partial responses, when treated with Tafinlar (dabrafenib) while 67% (4/6) receiving Tafinlar (dabrafenib) as a first-line treatment achieved partial responses (PMID: 27080216; NCT01336634). | 27080216 |
| BRAF V600E | lung non-small cell carcinoma | sensitive | BRAF Inhibitor | Dabrafenib | Guideline | Actionable | Tafinlar (dabrafenib) is in guidelines for patients with advanced or metastatic non-small cell lung cancer with BRAF V600E mutations who can not tolerate the combination of Mekinist (trametinib) and Tafinlar (dabrafenib) (NCCN.org). | detail... |
| BRAF V600E | ganglioglioma | predicted - sensitive | RAF Inhibitor (Pan) | Vemurafenib | Case Reports/Case Series | Actionable | In a Phase II trial (VE-BASKET), Zelboraf (vemurafenib) treatment resulted in a partial response in a patient with anaplastic ganglioglioma harboring BRAF V600E who stayed on treatment for 13.8 months (PMID: 30351999; NCT01524978). | 30351999 |
| BRAF V600E | colon cancer | sensitive | BRAF Inhibitor | GDC0879 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, GDC0879 inhibited survival of colon cancer cell lines harboring BRAF V600E in cell culture and cell line xenograft models (PMID: 19276360). | 19276360 |
| BRAF V600E | melanoma | predicted - sensitive | RAF Inhibitor (Pan) | Belvarafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Belvarafenib (HM95573) treatment led to inhibition of tumor growth in a melanoma cell line xenograft model harboring BRAF V600E (PMID: 33953400). | 33953400 |
| BRAF V600E | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor RAF Inhibitor (Pan) | RO5126766 | Preclinical - Cell culture | Actionable | In a preclinical study, RO5126766 inhibited proliferation of melanoma cells harboring BRAF V600E in culture (PMID: 26438159). | 26438159 |
| BRAF V600E | colorectal cancer | sensitive | BRAF Inhibitor | Cetuximab + PLX4720 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of PLX4720 and Erbitux (cetuximab) inhibited tumor growth in colorectal cancer cell line xenograft models harboring BRAF V600E (PMID: 22281684). | 22281684 |
| BRAF V600E | lung non-small cell carcinoma | sensitive | RAF Inhibitor (Pan) | TW-37 + Vemurafenib | Preclinical | Actionable | In a preclinical study, TW-37 enhanced the inhibitory effect of Zelboraf (vemurafenib) on human non-small cell lung cancer cells harboring BRAF V600E in culture (PMID: 25665005). | 25665005 |
| BRAF V600E | skin melanoma | no benefit | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib + YM-254890 | Preclinical - Cell culture | Actionable | In a preclinical study, combination treatment with YM-254890 and Mekinist (trametinib) did not result in synergistic inhibition of cell viability of a cutaneous melanoma cell line harboring BRAF V600E in culture (PMID: 33229459). | 33229459 |
| BRAF V600E | colorectal cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Selumetinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Selumetinib (AZD6244) decreased tumor growth in a cell line xenograft model of colorectal cancer harboring BRAF V600E (PMID: 23942066). | 23942066 |
| BRAF V600E | colorectal cancer | sensitive | BRAF Inhibitor | Encorafenib | Phase I | Actionable | In a Phase I trial, Encorafenib (LGX818) showed activity in patients with advanced metastatic colorectal cancer harboring a BRAF V600E mutation, resulting in a median progression-free survival of 4 months and a best response of stable disease in 66.7% (12/18) (Ann Oncol (2014) 25 (suppl 4): iv182-iv183). | detail... |
| BRAF V600E | colorectal cancer | sensitive | BRAF Inhibitor | PLX7904 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, PLX7904 inhibited survival of colorectal cancer cells harboring BRAF V600E in culture and demonstrated anti-tumor activity in cell line xenograft models (PMID: 26466569). | 26466569 |
| BRAF V600E | glioblastoma | sensitive | BRAF Inhibitor | BI2536 + PLX4720 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of BI 2536 and PLX4720 resulted in suppression of downstream signaling, increased apoptotic activity, inhibition of cell proliferation, and tumor growth suppression in glioblastoma cell line xenograft models harboring BRAF V600E (PMID: 26573800). | 26573800 |
| BRAF V600E | colorectal cancer | predicted - sensitive | RAF Inhibitor (Pan) | LSN3074753 | Preclinical - Pdx | Actionable | In a preclinical study, LSN3074753 demonstrated modest efficacy in patient-derived xenograft models of colorectal cancer harboring BRAF V600E, resulted in tumor growth inhibition or regression, but relapse upon discontinuation of treatment (PMID: 28611205). | 28611205 |
| BRAF V600E | rectum cancer | resistant | Cetuximab | Guideline | Actionable | Erbitux (cetuximab), as a monotherapy, is not indicated for use in rectum cancer patients with BRAF V600E (NCCN.org). | detail... | |
| BRAF V600E | ganglioglioma | sensitive | BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Guideline | Actionable | Combination of Mekinist (trametinib) and Tafinlar (dabrafenib) is included in guidelines as an adjuvant treatment for patients with ganglioglioma harboring BRAF V600E (NCCN.org). | detail... |
| BRAF V600E | melanoma | predicted - sensitive | BRAF Inhibitor | LXH 254 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600E was sensitive to treatment with LXH254, demonstrating inhibition of cell proliferation in culture, and inhibition of tumor growth and tumor regression in a cell line xenograft model of melanoma (PMID: 33355204). | 33355204 |
| BRAF V600E | melanoma | predicted - sensitive | BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + KRT-232 + Trametinib | Preclinical - Pdx | Actionable | In a preclinical study, the addition of KRT-232 (AMG 232) to the combination treatment of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in a synergistic effect, leading to a greater decrease in tumor growth and tumor size compared to either KRT-232 (AMG 232) alone or Tafinlar (dabrafenib) plus Mekinist (trametinib) in patient-derived xenograft (PDX) models of melanoma harboring BRAF V600E (PMID: 32234759). | 32234759 |
| BRAF V600E | colorectal cancer | sensitive | BRAF Inhibitor | BGB-283 | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, BGB-283 inhibited Braf phosphorylation and cell proliferation in colorectal cancer cell lines harboring BRAF V600E in culture, and resulted in partial tumor regression in both cell line and patient-derived xenograft models (PMID: 26208524). | 26208524 |
| BRAF V600E | melanoma | sensitive | RAF Inhibitor (Pan) | Navitoclax + Vemurafenib | Preclinical | Actionable | In a preclinical study, Navitoclax (ABT-263) enhanced the inhibitory effect of Zelboraf (vemurafenib) on human melanoma cells harboring BRAF V600E in culture (PMID: 25665005). | 25665005 |
| BRAF V600E | colorectal cancer | predicted - sensitive | BRAF Inhibitor | Dabrafenib + JSI-1187 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, combination treatment with Tafinlar (dabrafenib) and JSI-1187 led to synergistic inhibition of tumor growth in a colorectal cancer cell line xenograft model harboring BRAF V600E (Cancer Res 2020;80(16 Suppl):Abstract nr 4188). | detail... |
| BRAF V600E | thyroid gland cancer | sensitive | CLM3 | Preclinical | Actionable | In a preclinical study, CLM3 inhibited growth, Egfr signaling, and CCND1 expression in thyroid cancer cells harboring BRAF V600E in culture (PMID: 24423321). | 24423321 | |
| BRAF V600E | anaplastic astrocytoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor RAF Inhibitor (Pan) | Cobimetinib + Vemurafenib | Guideline | Actionable | Combination of Zelboraf (vemurafenib) and Cotellic (cobimetinib) is included in guidelines for patients with recurrent anaplastic gliomas harboring BRAF V600E, including anaplastic astrocytoma (NCCN.org). | detail... |
| BRAF V600E | melanoma | sensitive | ASTX029 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, ASTX029 treatment reduced Erk and Rsk phosphorylation, induced cell-cycle arrest, and inhibited growth of a melanoma cell line harboring BRAF V600E in culture and inhibited tumor growth in cell line xenograft models, and was also effective against cells with acquired resistance to Zelboraf (vemurafenib) or Koselugo (selumetinib) (PMID: 34330842). | 34330842 | |
| BRAF V600E | melanoma | sensitive | RAF Inhibitor (Pan) | DETD-35 + Vemurafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, DETD-35 and Zelboraf (vemurafenib) synergistically inhibited proliferation and colony formation of melanoma cells harboring BRAF V600E in culture and reduced tumor size in xenograft models (PMID: 27048951). | 27048951 |
| BRAF V600E | sarcoma | predicted - sensitive | RAF Inhibitor (Pan) | Vemurafenib | Case Reports/Case Series | Actionable | In a Phase II trial (VE-BASKET), responses were seen in sarcoma patients harboring BRAF V600E (n=6) when treated with Zelboraf (vemurafenib), including 1 patient with a complete response and 1 patient with a partial response (PMID: 32029534; NCT01524978). | 32029534 |
| BRAF V600E | melanoma | sensitive | BI-69A11 | Preclinical | Actionable | In a preclinical study, BI-69A11 inhibited proliferation and Akt/mTOR signaling in human melanoma cell lines harboring BRAF V600E in culture (PMID: 26603897, PMID: 20531415). | 20531415 26603897 | |
| BRAF V600E | ovarian cancer | predicted - sensitive | RAF Inhibitor (Pan) | Vemurafenib | Phase II | Actionable | In a Phase II trial (VE-BASKET), responses were seen in ovarian cancer patients harboring BRAF V600E (n=4) when treated with Zelboraf (vemurafenib), including 2 patients with a partial response (PMID: 32029534; NCT01524978). | 32029534 |
| BRAF V600E | ovarian cancer | predicted - sensitive | RAF Inhibitor (Pan) | Vemurafenib | Case Reports/Case Series | Actionable | In a Phase II trial (MyPathway), Zelboraf (vemurafenib) treatment resulted in an objective response of 50% (2/4, 2 partial response) in patients with ovarian cancer harboring BRAF V600E, and stable disease lasting more than 120 days in 1 patient (PMID: 29320312; NCT02091141). | 29320312 |
| BRAF V600E | colorectal cancer | sensitive | RAF Inhibitor (Pan) | Bevacizumab + Capecitabine + Vemurafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Zelboraf (vemurafenib) treatment when combined with Xeloda (capecitabine) and Avastin (bevacizumab) enhanced tumor growth inhibition and increased survival in a cell line xenograft model of colorectal cancer harboring BRAF V600E (PMID: 22180495). | 22180495 |
| BRAF V600E | colorectal cancer | sensitive | BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | BGB-283 + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination treatment of Mekinist (trametinib) and Lifirafenib (BGB-283) led to greater inhibition of growth in a colorectal cancer cell line harboring BRAF V600E in culture compared to either treatment alone (PMID: 33318037). | 33318037 |
| BRAF V600E | colorectal cancer | sensitive | BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + LXH 254 + Trametinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, combination treatment with LXH 254, Tafinlar (dabrafenib), and Mekinist (trametinib) in colorectal cancer cell lines harboring BRAF V600E resulted in suppression of colony formation in culture, and inhibition of tumor growth in a cell line xenograft model (PMID: 33568355). | 33568355 |
| BRAF V600E | glioblastoma | decreased response | BRAF Inhibitor | PLX4720 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, a glioblastoma cell line harboring BRAF V600E demonstrated a decreased response to treatment with PLX4720, demonstrating increased viability of CD133 positive cells in culture and in xenograft models (PMID: 26573800). | 26573800 |
| BRAF V600E | melanoma | sensitive | RAF Inhibitor (Pan) | C6-ceramide nanoliposome + Sorafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Nexavar (sorafenib) treatment in combination with C6-ceramide nanoliposome inhibited Mek and Akt phosphorylation, led to enhanced apoptosis and inhibition of proliferation, and synergistically reduced viability of melanoma cells harboring BRAF V600E in culture, and enhanced inhibition of tumor growth in a cell line xenograft model (PMID: 18519791). | 18519791 |
| BRAF V600E | colorectal cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor RAF Inhibitor (Pan) | Pimasertib + Sorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Pimasertib (MSC1936369B) and Nexavar (sorafenib) synergistically inhibited proliferation of colorectal cancer cells harboring BRAF V600E in culture (PMID: 23629727). | 23629727 |
| BRAF V600E | colorectal cancer | sensitive | BRAF Inhibitor | Cetuximab + Encorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, combination therapy consisting of Erbitux (cetuximab) and Encorafenib (LGX818) inhibited survival of colorectal cancer cell lines harboring BRAF V600E in culture (PMID: 27312529). | 27312529 |
| BRAF V600E | colorectal cancer | sensitive | BRAF Inhibitor | Cetuximab + Encorafenib | FDA approved - On Companion Diagnostic | Actionable | In a Phase III (BEACON CRC) trial that supported FDA approval, Braftovi (encorafenib) and Erbitux (cetuximab) combination treatment (n=113) resulted in improved median overall survival (8.4 vs 5.4 months, HR=0.60, p<0.001), confirmed response rate (20% vs 2%, p<0.001), and median progression-free survival (4.2 vs 1.5 months, HR=0.40, p<0.001) compared to control (n=107) in patients with metastatic colorectal cancer harboring BRAF V600E (PMID: 31566309; NCT02928224). | detail... 31566309 |
| BRAF V600E | glioblastoma | sensitive | Ulixertinib | Phase I | Actionable | In a Phase I trial, treatment with BVD-523 (Ulixertinib) resulted in a partial response in a patient with glioblastoma harboring BRAF V600E (PMID: 29247021). | 29247021 | |
| BRAF V600E | colorectal cancer | no benefit | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Panitumumab + Trametinib | Phase I | Actionable | In a Phase I trial, combination therapy consisting of Vectibix (panitumumab) and Mekinist (trametinib) resulted in an overall response rate of 0% (0/31), stable disease in 55% (17/31), and a median progression-free survival of 2.6 months in patients with BRAF V600E colorectal cancer (PMID: 29431699; NCT01750918). | 29431699 |
| BRAF V600E | colorectal cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Refametinib | Preclinical | Actionable | In a preclinical study, Refametinib (BAY86-9766) inhibited growth of colorectal cancer cell lines harboring BRAF V600E in culture and suppressed tumor growth in cell line xenograft models (PMID: 19706763). | 19706763 |
| BRAF V600E | Erdheim-Chester disease | sensitive | RAF Inhibitor (Pan) | Vemurafenib | Guideline | Actionable | Zelboraf (vemurafenib) is included in guidelines as preferred first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring BRAF V600E (NCCN Guidelines). | detail... |
| BRAF V600E | high grade glioma | predicted - sensitive | BRAF Inhibitor | Everolimus + PLX4720 | Preclinical - Cell culture | Actionable | In a preclinical study, Afinitor (everolimus) and PLX4720 synergistically inhibited growth and induced apoptosis in glioma cell lines in culture (PMID: 27217440). | 27217440 |
| BRAF V600E | colorectal cancer | sensitive | BRAF Inhibitor | Dabrafenib + SCH772984 | Preclinical - Cell culture | Actionable | In a preclinical study, combination therapy consisting of Tafinlar (dabrafenib) and SCH772984 inhibited survival of colorectal cancer cell lines harboring BRAF V600E in culture (PMID: 27312529). | 27312529 |
| BRAF V600E | melanoma | sensitive | BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | PLX4720 + Selumetinib | Preclinical | Actionable | In a preclinical study, PLX4720 and Selumetinib (AZD6244) worked synergistically to inhibit cell growth in PLX4720-resistant melanoma cell lines harboring BRAF V600E in culture (PMID: 26461489). | 26461489 |
| BRAF V600E | colorectal cancer | sensitive | RAF Inhibitor (Pan) | Cetuximab + Vemurafenib | Case Reports/Case Series | Actionable | In a clinical case study, the combination of Zelboraf (vemurafenib) and Erbitux (cetuximab) was tolerated and showed clinical benefit in a patient with BRAF V600E mutant colorectal cancer (PMID: 24523613). | 24523613 |
| BRAF V600E | colorectal cancer | sensitive | RAF Inhibitor (Pan) | Cetuximab + Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Zelboraf (vemurafenib) and Erbitux (cetuximab) combination treatment inhibited survival of colorectal cancer cell lines harboring BRAF V600E in culture (PMID: 27312529). | 27312529 |
| BRAF V600E | colorectal cancer | sensitive | RAF Inhibitor (Pan) | Cetuximab + Vemurafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Zelboraf (vemurafenib) treatment in combination with Erbitux (cetuximab) enhanced tumor growth inhibition and increased survival in a cell line xenograft model of colorectal cancer harboring BRAF V600E (PMID: 22180495). | 22180495 |
| BRAF V600E | hairy cell leukemia | sensitive | RAF Inhibitor (Pan) | Vemurafenib | Phase II | Actionable | In two Phase II clinical studies, patients with refractory hairy cell leukemia harboring BRAF V600E responded to Zelboraf (vemurafenib) with overall response rates of 96% (25/26) and 100% (24/24) as well as complete response rates of 35% (9/26) and 42% (10/24) with median follow up times of 8 and 12 weeks, respectively (PMID: 26352686). | 26352686 |
| BRAF V600E | thyroid gland papillary carcinoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor RAF Inhibitor (Pan) | RO5126766 | Preclinical | Actionable | In a preclinical study, RO5126766 inhibited Mek signaling and increased radioiodide uptake and response in transgenic animal models of papillary thyroid carcinoma driven by BRAF V600E (PMID: 27669459). | 27669459 |
| BRAF V600E | melanoma | sensitive | S3I-201 | Preclinical | Actionable | In a preclinical study, S3I-201 inhibited cell invasion and Stat3 signaling in human melanoma cell lines harboring BRAF V600E that are resistant to Braf inhibition in culture (PMID: 23242808). | 23242808 | |
| BRAF V600E | thyroid gland papillary carcinoma | sensitive | RAF Inhibitor (Pan) | Vemurafenib | Case Reports/Case Series | Actionable | In a Phase I trial, Zelboraf (vemurafenib) treatment resulted in a complete or partial response in three papillary thyroid carcinoma patients harboring BRAF V600E, with one patient having a response that lasted for 8 months who remained progression-free for 12 months, and another two patients having a stable disease that lasted for 11 and 13 months, respectively (PMID: 20818844; NCT00215605). | 20818844 |
| BRAF V600E | thyroid gland papillary carcinoma | sensitive | RAF Inhibitor (Pan) | Vemurafenib | Guideline | Actionable | Zelboraf (vemurafenib) is included in guidelines for patients with recurrent, advanced, or metastatic thyroid papillary carcinoma harboring BRAF V600E for whom clinical trials are not available or appropriate (NCCN.org). | detail... |
| BRAF V600E | thyroid gland papillary carcinoma | sensitive | RAF Inhibitor (Pan) | Vemurafenib | Phase II | Actionable | In a Phase II trial, Zelboraf (vemurafenib) treatment resulted in a partial response in 38.5% (10/26) of patients with metastatic or unresectable, radioactive iodine-refractory papillary thyroid carcinoma harboring BRAF V600E that were multikinase inhibitor-naive, with a disease control rate of 73%, and a median progression-free survival of 18.2 months (PMID: 27460442; NCT01286753). | 27460442 |
| BRAF V600E | colon cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Navitoclax + Trametinib | Preclinical | Actionable | In a preclinical study, Navitoclax (ABT-263) enhanced the inhibitory effect of Mekinist (trametinib) on human colon cancer cells harboring BRAF V600E in culture (PMID: 25665005). | 25665005 |
| BRAF V600E | colon cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | PD-0325901 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, PD-0325901 demonstrated antitumor activity against BRAF V600E colon cancer cell line xenografts (PMID: 16273091). | 16273091 |
| BRAF V600E | melanoma | sensitive | BRAF Inhibitor | GDC0879 | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, GDC0879 inhibited survival of melanoma cell lines harboring BRAF V600E in cell culture, cell line xenograft and patient-derived xenograft (PDX) models (PMID: 19276360). | 19276360 |
| BRAF V600E | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor RAF Inhibitor (Pan) | Cobimetinib + Vemurafenib | FDA approved - On Companion Diagnostic | Actionable | In a Phase III trial (coBRIM) that supported FDA approval, treatment with the combination of Zelboraf (vemurafenib) and Cotellic (cobimetinib) resulted in an improved progression-free survival of 12.3 months, compared to 7.2 months with Zelboraf (vemurafenib) plus placebo, among patients with BRAF V600-mutated metastatic melanoma, and BRAF V600E and BRAF V600K are on the companion diagnostic (PMID: 27480103; NCT01689519). | 27480103 detail... detail... |
| BRAF V600E | Advanced Solid Tumor | sensitive | BRAF Inhibitor | RAF265 | Preclinical | Actionable | In a preclinical study, RAF265 inhibited Erk phosphorylation and cell proliferation in BRAF V600E expressing cells in culture (PMID: 20538618). | 20538618 |
| BRAF V600E | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Refametinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Refametinib (BAY86-9766) inhibited growth of melanoma cell lines harboring BRAF V600E in culture and suppressed tumor growth in cell line xenograft models (PMID: 19706763). | 19706763 |
| BRAF V600E | Advanced Solid Tumor | sensitive | BRAF Inhibitor | SB590885 | Preclinical | Actionable | In a preclinical study, SB590885 inhibited inhibited Erk phosphorylation and cell proliferation of transformed cells expression BRAF V600E in culture (PMID: 20538618). | 20538618 |
| BRAF V600E | colorectal cancer | predicted - sensitive | RAF Inhibitor (Pan) | Belvarafenib | Case Reports/Case Series | Actionable | In a Phase I trial, Belvarafenib (HM95573) treatment in a colorectal cancer patient harboring BRAF V600E led to a tumor reduction of 39% after 8 weeks of treatment and a confirmed partial response at 12 weeks, and response to treatment was maintained for 8 weeks (PMID: 33953400; NCT03118817). | 33953400 |
| BRAF V600E | colorectal cancer | no benefit | RAF Inhibitor (Pan) | Vemurafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, colorectal cancer cell lines were not sensitive to growth inhibition by Zelboraf (vemurafenib) in culture or xenograft models, due to feedback activation of EGFR signaling (PMID: 22281684). | 22281684 |
| BRAF V600E | colorectal cancer | no benefit | RAF Inhibitor (Pan) | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, colorectal cancer cell lines harboring BRAF V600E demonstrated decreased response to Zelboraf (vemurafenib) in culture (PMID: 27312529). | 27312529 |
| BRAF V600E | colorectal cancer | no benefit | RAF Inhibitor (Pan) | Vemurafenib | Phase II | Actionable | In a Phase II trial, Zelboraf (vemurafenib) did not demonstrate meaningful clinical activity as a single agent, resulted in partial response in 5% (1/21) and stable disease in 33% (7/21) of patients with metastatic colorectal cancer harboring BRAF V600E (PMID: 26460303; NCT00405587). | 26460303 |
| BRAF V600E | salivary gland carcinoma | predicted - sensitive | BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case report, combined Tafinlar (dabrafenib) and Mekinist (trametinib) treatment of a patient with salivary duct carcinoma harboring BRAF V600E resulted in a reduction of metastatic lesions and stable disease lasting 13 months followed by disease progression (PMID: 30323086). | 30323086 |
| BRAF V600E | glioblastoma | sensitive | BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Phase II | Actionable | In a Phase II trial (ROAR), Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment resulted in an objective response in 32% (10/31, 2 complete responses, 8 partial responses) and stable disease in 19% (6/31) of patients with glioblastoma harboring BRAF V600E (PMID: 34838156; NCT02034110). | 34838156 |
| BRAF V600E | glioblastoma | sensitive | BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, Mekinist (trametinib) and Tafinlar (dabrafenib) combination treatment resulted in a complete resolution of symptoms and radiographic partial response after the first treatment in a patient with glioblastoma harboring BRAF V600E whose disease progressed on PLX8394 treatment, and a complete response after 11 months of treatment, CDKN2A/B loss and CHEK2 T367fs were also identified in the tumor (PMID: 32923904). | 32923904 |
| BRAF V600E | glioblastoma | sensitive | BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, combination therapy of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in improved clinical symptoms in a patient with epithelioid glioblastoma harboring BRAF V600E, and treatment of the patient's cells resulted in decreased cell viability, reduced phosphorylation of Mek and Erk, increased apoptotic activity compared to either agent alone, and cell cycle arrest in culture, and led to tumor growth suppression in the patient-derived xenograft (PDX) model (PMID: 31345255). | 31345255 |
| BRAF V600E | glioblastoma | sensitive | BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, Mekinist (trametinib) and Tafinlar (dabrafenib) combination treatment resulted in significant clinical improvement in a patient with epithelioid glioblastoma harboring BRAF V600E, however, her disease progressed after 3 months of therapy (PMID: 31217909). | 31217909 |
| BRAF V600E | glioblastoma | sensitive | BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Guideline | Actionable | Combination of Mekinist (trametinib) and Tafinlar (dabrafenib) is included in guidelines for patients with recurrent glioblastoma harboring BRAF V600E (NCCN.org). | detail... |
| BRAF V600E | glioblastoma | sensitive | BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, an epithelioid glioblastoma patient harboring BRAF V600E treated with Mekinist (trametinib) and Tafinlar (dabrafenib) combination therapy resulted in stable disease, and the patient continued to demonstrate stable disease at least 16 months after initiation of therapy (PMID: 29632053). | 29632053 |
| BRAF V600E | biliary tract cancer | sensitive | BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Phase II | Actionable | In a Phase II trial, Tafinlar (dabrafenib) in combination with Mekinist (trametinib) demonstrated a manageable safety profile, and resulted in an overall response rate of 51% (22/43, all partial responses) in patients with biliary tract cancer harboring BRAF V600E, with a median duration of response of 9 months, a median progression-free survival of 9 months, and a median overall survival of 14 months (PMID: 32818466; NCT02034110). | 32818466 |
| BRAF V600E | biliary tract cancer | sensitive | BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Guideline | Actionable | Tafinlar (dabrafenib) in combination with Mekinist (trametinib) is included in guidelines as subsequent-line therapy for patients with biliary tract cancer harboring BRAF V600E (NCCN.org). | detail... |
| BRAF V600E | melanoma | sensitive | BRAF Inhibitor | Gefitinib + PLX4720 | Preclinical | Actionable | In a preclinical study, Iressa (gefitinib) in combination with PLX4720 inhibited proliferation and tumorigenicity in human melanoma cell line harboring BRAF V600E and resistant to Braf inhibition in culture and in animal models (PMID: 23242808). | 23242808 |
| BRAF V600E | colorectal cancer | sensitive | RAF Inhibitor (Pan) | Gefitinib + Vemurafenib | Preclinical | Actionable | In a preclinical study, the combination of Zelboraf (vemurafenib) and Iressa (gefitinib) decreased the number of viable colorectal cancer cells harboring a BRAF V600E mutation in cell culture (PMID: 22448344). | 22448344 |
| BRAF V600E | endometrial adenocarcinoma | predicted - sensitive | BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Rabeprazole + Rifampin + Trametinib | Case Reports/Case Series | Actionable | In a Phase I trial, the addition of Mekinist (trametinib) to the combination treatment with Tafinlar (dabrafenib), Rabeprazol, and Rifampin resulted in a maintained radiographic response of lung metastases and stable pelvic mass size in a patient with metastatic endometrial adenocarcinoma harboring BRAF V600E, which lasted for 12 months (PMID: 33537843; NCT01954043). | 33537843 |
| BRAF V600E | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | RO4987655 | Preclinical - Cell culture | Actionable | In a preclinical study, RO4987655 inhibited proliferation of melanoma cells harboring BRAF V600E in culture (PMID: 26438159). | 26438159 |
| BRAF V600E | colorectal cancer | sensitive | RAF Inhibitor (Pan) | Erlotinib + Vemurafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Zelboraf (vemurafenib) treatment in combination with Tarceva (erlotinib) enhanced tumor growth inhibition and increased survival in a cell line xenograft model of colorectal cancer harboring BRAF V600E compared to either agent alone (PMID: 22180495). | 22180495 |
| BRAF V600E | colorectal cancer | sensitive | RAF Inhibitor (Pan) | Erlotinib + Vemurafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of Zelboraf (vemurafenib) and Tarceva (erlotinib) resulted in improved inhibition of tumor growth in BRAF V600E mutant human colon cancer cell line xenograft models compared to either drug as monotherapy (PMID: 22448344). | 22448344 |
| BRAF V600E | colorectal cancer | sensitive | RAF Inhibitor (Pan) | CCT196969 | Preclinical - Cell culture | Actionable | In a preclinical study, CCT196969 inhibited growth of BRAF-mutant colorectal cancer cell lines in culture (PMID: 25500121), which have been reported to harbor BRAF V600E (PMID: 15294323). | 25500121 15294323 |
| BRAF V600E | colorectal cancer | predicted - sensitive | BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Panitumumab + Trametinib | Phase I | Actionable | In a Phase I trial, combination therapy consisting of Tafinlar (dabrafenib), Vectibix (panitumumab), and Mekinist (trametinib) resulted in an overall response rate of 21% (19/91, 1 complete response, 18 partial response), stable disease in 65% (59/91), and a median progression-free survival of 4.2 months in patients with BRAF V600E colorectal cancer (PMID: 29431699; NCT01750918). | 29431699 |
| BRAF V600E | colorectal cancer | sensitive | BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Cetuximab + Dabrafenib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, combination therapy consisting of Erbitux (cetuximab), Tafinlar (dabrafenib), and Mekinist (trametinib) inhibited survival of colorectal cancer cell lines harboring BRAF V600E in culture (PMID: 27312529). | 27312529 |
| BRAF V600E | lung cancer | sensitive | Ulixertinib | Phase I | Actionable | In a Phase I trial, treatment with BVD-523 (ulixertinib) resulted in a partial response in two patients with lung cancer each harboring BRAF V600E (PMID: 29247021). | 29247021 | |
| BRAF V600E | melanoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | U0126 | Preclinical - Cell culture | Actionable | In a preclinical study, U0126 treatment inhibited Erk phosphorylation and reduced growth of melanoma cells harboring BRAF V600E in culture (PMID: 18794803). | 18794803 |
| BRAF V600E | high grade glioma | predicted - sensitive | RAF Inhibitor (Pan) | Belvarafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Belvarafenib (HM95573) treatment led to inhibition of cell viability in a patient-derived glioma cell line harboring BRAF V600E in culture (PMID: 34433654). | 34433654 |
| BRAF V600E | triple-receptor negative breast cancer | predicted - sensitive | RAF Inhibitor (Pan) | Nab-paclitaxel + Vemurafenib | Case Reports/Case Series | Actionable | In a clinical case study, Zelboraf (vemurafenib) and Abraxane (nab-paclitaxel) combination treatment resulted in regression of some metastatic pulmonary lesions and a progression-free survival of 4.4 months in a patient with triple-negative breast cancer harboring BRAF V600E, but a biopsy in lesions that progressed showed acquisition of additional mutations in PDGFRB, NF2, GRM3, MLH1, FOXA1, LRP1B, and AR amplification (PMID: 34818649). | 34818649 |
| BRAF V600E | Advanced Solid Tumor | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Phase II | Actionable | In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment resulted in an objective response rate of 37.9% (11/29) in patients with BRAF V600E positive advanced solid tumors other than melanoma, thyroid cancer, or colorectal cancer, with a median duration of response of 25.1 months, and a disease control rate of 75.9% (22/29) (PMID: 32758030; NCT02465060). | 32758030 |
| BRAF V600E | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Palbociclib + PD-0325901 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination treatment of PD-0325901 and Ibrance (palbociclib) resulted in significant tumor regression in melanoma cell line xenograft models harboring BRAF V600E and demonstrated a 56% (5/9) complete response rate (PMID: 27488531). | 27488531 |
| BRAF V600E | glioblastoma | sensitive | BI2536 | Preclinical - Cell culture | Actionable | In a preclinical study, a glioblastoma cell line harboring BRAF V600E demonstrated sensitivity to BI2536 in culture (PMID: 26573800). | 26573800 | |
| BRAF V600E | lung non-small cell carcinoma | not predictive | Pembrolizumab | Clinical Study - Cohort | Actionable | In a retrospective analysis, non-small cell lung cancer patients harboring BRAF V600E did not demonstrate a significantly different response to treatment with either Keytruda (pembrolizumab), Opdivo (nivolumab), or Tecentriq (atezolizumab), compared to patients with BRAF non-V600E mutations, demonstrating an objective response rate of 25% (3/12) vs 33% (3/9) (p=1.0) and median progression-free survival of 3.7 months vs 4.1 months (p=0.37) (PMID: 29723688). | 29723688 | |
| BRAF V600E | anaplastic oligodendroglioma | sensitive | BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Guideline | Actionable | Combination of Mekinist (trametinib) and Tafinlar (dabrafenib) is included in guidelines for patients with recurrent anaplastic gliomas harboring BRAF V600E, including anaplastic oligodendroglioma (NCCN.org). | detail... |
| BRAF V600E | melanoma | sensitive | RAF Inhibitor (Pan) | INU-152 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, INU-152 reduced MEK and ERK phosphorylation and growth of a melanona cell line harboring BRAF V600E in culture, and inhibited tumor growth in xenograft models (PMID: 28645859). | 28645859 |
| BRAF V600E | melanoma | sensitive | BRAF Inhibitor | Doxorubicin + PLX4720 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of PLX4720 and Adriamycin (doxorubicin) resulted in antitumor efficacy in a melanoma cell line harboring BRAF V600E, demonstrating decreased cell survival and increased apoptotic activity in xenograft models, and inhibition of cell growth in culture (PMID: 27924459). | 27924459 |
| BRAF V600E | thyroid gland papillary carcinoma | predicted - sensitive | BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, a papillary thyroid carcinoma patient who progressed on Lenvima (lenvatinib) was found to harbor BRAF V600E and was treated with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) on a clinical trial, resulting in partial response in the thyroid bed, cervical and intrathoracic lymph nodes, and pulmonary lesions, with a decrease in target lesion size of 67%, and the patient remained on treatment for 18 months before stopping due to progression (PMID: 31085763). | 31085763 |
| BRAF V600E | melanoma | sensitive | BRAF Inhibitor | PLX4720 + Tivozanib | Preclinical | Actionable | In a preclinical study, PLX4720 and Tivozanib (AV-951) worked synergistically to inhibit cell growth in PLX4720-resistant melanoma cell lines harboring BRAF V600E in culture (PMID: 26461489). | 26461489 |
| BRAF V600E | colorectal adenocarcinoma | sensitive | DEL-22379 | Preclinical - Pdx | Actionable | In a preclinical study, DEL-22379 inhibited tumor growth in a colorectal adenocarcinoma patient-derived xenograft model harboring BRAF V600E (PMID: 26267534). | 26267534 | |
| BRAF V600E | melanoma | sensitive | BRAF Inhibitor | Erlotinib + PLX4720 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of PLX4720 and Tarceva (erlotinib) resulted in antitumor efficacy in a melanoma cell line harboring BRAF V600E, demonstrating decreased cell survival and increased apoptotic activity in xenograft models and culture (PMID: 27924459). | 27924459 |
| BRAF V600E | colorectal cancer | predicted - resistant | BI-3406 | Preclinical - Cell culture | Actionable | In a preclinical study, BI-3406 treatment failed to inhibit growth of colorectal cancer cells harboring BRAF V600E in culture (PMID: 32816843). | 32816843 | |
| BRAF V600E | pleomorphic xanthoastrocytoma | sensitive | BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, Mekinist (trametinib) and Tafinlar (dabrafenib) combination treatment resulted in clinical benefit that lasted for more than 14 months in a patient with pleomorphic xanthoastrocytoma harboring BRAF V600E (PMID: 29632053). | 29632053 |
| BRAF V600E | pleomorphic xanthoastrocytoma | sensitive | BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Guideline | Actionable | Mekinist (trametinib) and Tafinlar (dabrafenib) combination therapy is included in guidelines as an adjuvant treatment for patients with pleomorphic xanthoastrocytoma harboring BRAF V600E (NCCN.org). | detail... |
| BRAF V600E | melanoma | sensitive | SCH772984 | Preclinical | Actionable | In a preclinical study, SCH772984 inhibited growth of melanoma cell lines harboring BRAF V600E in culture (PMID: 26267534). | 26267534 | |
| BRAF V600E | melanoma | sensitive | BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + RAF709 + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, combination treatment with RAF709, Tafinlar (dabrafenib), and Mekinist (trametinib) in melanoma cell line harboring BRAF V600E resulted in suppression of colony formation in culture (PMID: 33568355). | 33568355 |
| BRAF V600E | melanoma | sensitive | RAF Inhibitor (Pan) | TW-37 + Vemurafenib | Preclinical | Actionable | In a preclinical study, TW-37 enhanced the inhibitory effect of Zelboraf (vemurafenib) on human melanoma cells harboring BRAF V600E in culture (PMID: 25665005). | 25665005 |
| BRAF V600E | skin melanoma | sensitive | RAF Inhibitor (Pan) | Vemurafenib | Guideline | Actionable | Zelboraf (vemurafenib) therapy is included in guidelines for cutaneous melanoma patients with unresectable or metastatic disease harboring BRAF V600 activating mutations, such as BRAF V600E, in cases where BRAF/MEK inhibitor combination therapy is contraindicated (NCCN.org). | detail... |
| BRAF V600E | colorectal cancer | sensitive | RAF Inhibitor (Pan) | Sorafenib | Preclinical | Actionable | In a preclinical study, colorectal cancer cell lines harboring a BRAF V600E mutation were sensitive to Nexavar (sorafenib) in culture (PMID: 24885690). | 24885690 |
| BRAF V600E | colorectal cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | PD-0325901 | Preclinical | Actionable | In a preclinical study, PD-0325901 inhibited growth of colorectal cancer cell lines harboring BRAF V600E in culture (PMID: 26267534). | 26267534 |
| BRAF V600E | melanoma | sensitive | BRAF Inhibitor | PLX8394 | Preclinical - Cell culture | Actionable | In a preclinical study, PLX8394 treatment inhibited Erk phosphorylation and reduced proliferation of melanoma cells harboring either monomeric BRAF V600E or dimeric isoform (p61) of V600E in culture (PMID: 30559419). | 30559419 |
| BRAF V600E | melanoma | sensitive | RAF Inhibitor (Pan) | CCT241161 | Preclinical - Pdx | Actionable | In a preclinical study, CCT241161 inhibited growth of a human melanoma cell line harboring BRAF V600E in culture, and induced tumor regression in several BRAF V600E-mutant melanoma patient-derived xenograft models (PMID: 25500121). | 25500121 |
| BRAF V600E | high grade glioma | sensitive | RAF Inhibitor (Pan) | LY3009120 + Vemurafenib | Preclinical - Patient cell culture | Actionable | In a preclinical study, combination treatment with Zelboraf (vemurafenib) and LY3009120 treatment led to greater inhibition of cell growth compared to either agent alone in a patient-derived glioma cell line harboring BRAF V600E in culture (PMID: 34433654). | 34433654 |
| BRAF V600E | colon neuroendocrine neoplasm | predicted - sensitive | BRAF Inhibitor | Dabrafenib | Case Reports/Case Series | Actionable | In a clinical case study, Tafinlar (dabrafinib) treatment of a patient with recurrent neuroendocrine carcinoma of the colon harboring a BRAF V600E mutation resulted in stable disease for 6 months before disease progression (PMID: 30181415). | 30181415 |
| BRAF V600E | thyroid gland cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Selumetinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Selumetinib (AZD6244) inhibited growth of both parental thyroid cancer cell lines harboring BRAF V600E and those acquired Sprycel (dasatinib)-resistance in culture (PMID: 27222538). | 27222538 |
| BRAF V600E | melanoma | sensitive | BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | BI 882370 + Trametinib | Preclinical | Actionable | In a preclinical study, xenograft models of melanoma harboring BRAF V600E treated with the combination of BI 882370 and Mekinist (trametinib) demonstrated tumor regression with no regrowth during the 5 weeks of treatment (PMID: 26916115). | 26916115 |
| BRAF V600E | melanoma | sensitive | BRAF Inhibitor | Alpelisib + PLX4720 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of Alpelisib (BYL719) and PLX4720 enhanced antitumor activity in a melanoma cell line harboring BRAF V600E, demonstrating decreased cell survival and increased apoptotic activity in xenograft models, and decreased Akt signaling in culture (PMID: 27924459). | 27924459 |
| BRAF V600E | melanoma | sensitive | RAF Inhibitor (Pan) | LY3009120 | Preclinical - Cell culture | Actionable | In a preclinical study, LY3009120 treatment inhibited Erk phosphorylation and reduced proliferation of a melanoma cells harboring either monomeric BRAF V600E or dimeric isoform (p61) of V600E in culture (PMID: 30559419). | 30559419 |
| BRAF V600E | melanoma | sensitive | RAF Inhibitor (Pan) | LY3009120 | Preclinical | Actionable | In a preclinical study, LY3009120 inhibited growth, downstream MAPK signaling and soft agar growth in human melanoma cell lines harboring BRAF V600E in culture (PMID: 26343583). | 26343583 |
| BRAF V600E | larynx cancer | predicted - sensitive | RAF Inhibitor (Pan) | Vemurafenib | Case Reports/Case Series | Actionable | In a Phase II trial (MyPathway), Zelboraf (vemurafenib) treatment resulted in complete response in a patient with larynx cancer harboring BRAF V600E (PMID: 29320312; NCT02091141). | 29320312 |
| BRAF V600E | glioblastoma | predicted - sensitive | BRAF Inhibitor | PLX8394 | Case Reports/Case Series | Actionable | In a clinical case study, PLX8349 treatment resulted in a radiographic partial response and complete resolution of symptoms for 7 months in a patient with glioblastoma harboring BRAF V600E, CDKN2A/B loss and CHEK2 T367fs were also identified in the tumor (PMID: 32923904; NCT02428712). | 32923904 |
| BRAF V600E | Advanced Solid Tumor | sensitive | BRAF Inhibitor | PLX4720 | Preclinical | Actionable | In a preclinical study, PLX4720 inhibited Erk phosphorylation and cell proliferation of transformed cells expression BRAF V600E in culture (PMID: 20538618). | 20538618 |
| BRAF V600E | Advanced Solid Tumor | sensitive | BRAF Inhibitor | BGB-283 | Preclinical - Cell culture | Actionable | In a preclinical study, BGB-283 inhibited viability of a variety of cancer cell lines harboring BRAF V600E in culture (PMID: 26208524). | 26208524 |
| BRAF V600E | lung non-small cell carcinoma | unknown | unspecified immune checkpoint inhibitor | Clinical Study - Cohort | Actionable | In a retrospective clinical study, patients with non-small cell lung cancer harboring rare targetable drivers (RTD) (BRAF, ERBB2/3, RET, MET, ROS1, NTRK) who received immune checkpoint inhibitors (ICI) achieved longer median overall survival (mOS) (32 vs 13 mo, p=0.01) compared to those who did not receive ICI, mOS was not reached in patients harboring BRAF V600E (n=5) mutations, although RTD type was not associated with OS in a univariate analysis (PMID: 30268448). | 30268448 | |
| BRAF V600E | colorectal cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor RAF Inhibitor (Pan) | Cobimetinib + Vemurafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of Cotellic (cobimetinib) and Zelboraf (vemurafenib) inhibited tumor growth in a cell line xenograft model of colorectal cancer harboring BRAF V600E (PMID: 28649441). | 28649441 |
| BRAF V600E | colorectal cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Chloroquine + Trametinib | Preclinical - Pdx | Actionable | In a preclinical study, combination treatment with Mekinist (trametinib) and Chloroquine resulted in tumor regression in a colorectal cancer patient-derived xenograft (PDX) model harboring BRAF V600E (PMID: 30833748). | 30833748 |
| BRAF V600E | thyroid gland cancer | sensitive | RAF Inhibitor (Pan) | Lapatinib + Vemurafenib | Preclinical | Actionable | In a preclinical study, the combination of Tykerb (lapatinib) and Zelboraf (vemurafenib) inhibited growth of thyroid cancer cells harboring a BRAF V600E mutation in culture and in BRAF-mutant mouse models of thyroid cancer (PMID: 23365119). | 23365119 |
| BRAF V600E | pancreatic endocrine carcinoma | predicted - sensitive | RAF Inhibitor (Pan) | Vemurafenib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with pancreatic endocrine carcinoma found to harbor BRAF V600E demonstrated stable disease and some tumor shrinkage when treated with Zelboraf (vemurafenib) (PMID: 31158244). | 31158244 |
| BRAF V600E | melanoma | sensitive | BRAF Inhibitor | RXDX-105 | Preclinical - Cell line xenograft | Actionable | In preclinical studies, CEP-32496 (RXDX-105) reduced tumor volume and promoted tumor regression in xenograft models of a BRAF V600E mutant human melanoma cell line (PMID: 22319199). | 22319199 |
| BRAF V600E | melanoma | sensitive | BRAF Inhibitor | Encorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Braftovi (encorafenib) treatment inhibited Erk phosphorylation and reduced proliferation of melanoma cells harboring monomeric BRAF V600E in culture (PMID: 30559419). | 30559419 |
| BRAF V600E | melanoma | sensitive | BRAF Inhibitor | Encorafenib | Preclinical - Cell line xenograft | Actionable | In preclinical studies, Encorafenib (LGX818) treatment of human melanoma xenograft models with BRAF V600E significantly decreased Mek activation and resulted in tumor regression (Cancer Res: 72(8) Suppl 1, Abstract #3790). | detail... |
| BRAF V600E | melanoma | sensitive | BRAF Inhibitor | RAF709 | Preclinical - Cell culture | Actionable | In a preclinical study, RAF709 inhibited Erk signaling and proliferation of melanoma cells harboring BRAF V600E in culture (PMID: 29343524). | 29343524 |
| BRAF V600E | lung adenocarcinoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Case Reports/Case Series | Actionable | In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment resulted in an objective response rate of 37.9% (11/29) in patients with advanced solid tumors harboring BRAF V600E, of 4 patients with lung adenocarcinoma, 1 achieved a partial response with an ongoing progression-free survival (PFS) at 32.5 mo, 3 patients had stable disease for 15.6, 6.6, and 3.6 mo, and an additional unevaluable patient achieved an 81% reduction of measured lesions and a PFS of 12.7 mo (PMID: 32758030; NCT02465060). | 32758030 |
| BRAF V600E | melanoma | no benefit | SHP099 | Preclinical | Actionable | In a preclinical study, SHP099 did not inhibit proliferation or ERK activation in a melanoma cell line harboring BRAF V600E in culture (PMID: 27362227). | 27362227 | |
| BRAF V600E | melanoma | sensitive | BRAF Inhibitor | PLX7904 | Preclinical - Cell culture | Actionable | In a preclinical study, PLX7904 inhibited survival of melanoma cell lines harboring monomeric BRAF V600E as well as cells harboring the Zelboraf (vemurafenib)-resistant dimeric BRAF V600E in culture (PMID: 26466569). | 26466569 |
| BRAF V600E | thyroid gland papillary carcinoma | sensitive | BRAF Inhibitor | Dabrafenib | Clinical Study - Cohort | Actionable | In a clinical study, Tafinlar (dabrafenib) treatment stimulated radioiodine uptake in 60% (6/10) of patients with metastatic iodine-refractory papillary thyroid cancer harboring BRAF V600E (PMID: 25549723; NCT01534897). | 25549723 |
| BRAF V600E | thyroid gland papillary carcinoma | sensitive | BRAF Inhibitor | Dabrafenib | Guideline | Actionable | Tafinlar (dabrafenib) is included in guidelines for patients with recurrent, advanced, or metastatic thyroid papillary carcinoma harboring BRAF V600E for whom clinical trials are not available or appropriate (NCCN.org). | detail... |
| BRAF V600E | lung non-small cell carcinoma | sensitive | BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | FDA approved - On Companion Diagnostic | Actionable | In a Phase II trial that supported FDA approval, treatment with the combination of Mekinist (trametinib) and Tafinlar (dabrafenib) in patients with non-small cell lung cancer harboring BRAF V600E resulted in an overall response rate of 66.7% (38/57) in previously treated patients and 64% (23/36) in untreated patients, versus 33% (26/78) treated with Tafinlar (dabrafenib) alone (PMID: 27080216, PMID: 27283860, PMID: 28919011; NCT01336634). | 27283860 detail... 27080216 detail... detail... 28919011 |
| BRAF V600E | lung non-small cell carcinoma | sensitive | BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Guideline | Actionable | Combination of Mekinist (trametinib) and Tafinlar (dabrafenib) is in guidelines for metastatic non-small cell lung cancer patients with BRAF V600E mutations (NCCN.org). | detail... |
| BRAF V600E | melanoma | sensitive | BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | BGB-283 + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination treatment of Mekinist (trametinib) and Lifirafenib (BGB-283) led to greater inhibition of growth in melanoma cell lines harboring BRAF V600E in culture compared to either treatment alone (PMID: 33318037). | 33318037 |
| BRAF V600E | melanoma | sensitive | BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Regorafenib + Trametinib | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, combination treatment with Stivarga (regorafenib), Tafinlar (dabrafenib), and Mekinist (trametinib) in a melanoma cell line harboring BRAF V600E resulted in suppression of colony formation in culture, and suppressed tumor growth in patient-derived xenograft (PDX) models (PMID: 33568355). | 33568355 |
| BRAF V600E | melanoma | sensitive | RAF Inhibitor (Pan) | ASTX029 + Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, combination treatment with ASTX029 and Zelboraf (vemurafenib) resulted in decreased viability of melanoma cells harboring BRAF V600E compared to either agent alone in culture (PMID: 34330842). | 34330842 |
| BRAF V600E | colorectal cancer | predicted - sensitive | BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib + Cetuximab + Encorafenib | Phase III | Actionable | In a Phase III (BEACON CRC) trial, Braftovi (encorafenib), Mektovi (binimetinib), and Erbitux (cetuximab) combination treatment (n=111) resulted in improved median overall survival (9.0 vs 5.4 months, HR=0.52, p<0.001), confirmed response rate (26% vs 2%, p<0.001), and median progression-free survival (4.3 vs 1.5 months, HR=0.38, p<0.001) compared to control (n=107) in patients with metastatic colorectal cancer harboring BRAF V600E (PMID: 31566309; NCT02928224). | 31566309 |
| BRAF V600E | melanoma | sensitive | BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + LXH 254 + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, combination treatment with LXH 254, Tafinlar (dabrafenib), and Mekinist (trametinib) in a melanoma cell line harboring BRAF V600E resulted in suppression of colony formation in culture (PMID: 33568355). | 33568355 |
| BRAF V600E | rectum cancer | sensitive | BRAF Inhibitor | Cetuximab + Encorafenib | Guideline | Actionable | Braftovi (encorafenib) in combination with Erbitux (cetuximab) is included in guidelines as primary or subsequent therapy for patients with rectal cancer harboring BRAF V600E (NCCN.org). | detail... |
| BRAF V600E | glioblastoma | predicted - sensitive | RAF Inhibitor (Pan) | Vemurafenib | Case Reports/Case Series | Actionable | In a Phase II trial (VE-BASKET), Zelboraf (vemurafenib) treatment resulted in stable disease as best response in 3 of 6 patients with glioblastoma harboring BRAF V600E, with stable disease lasting 3.6, 3.7, and 12.9 months, respectively (PMID: 30351999; NCT01524978). | 30351999 |
| BRAF V600E | glioblastoma | predicted - sensitive | RAF Inhibitor (Pan) | Vemurafenib | Case Reports/Case Series | Actionable | In a clinical case study, Zelboraf (vemurafenib) treatment resulted in a partial response 1 week after treatment in a patient with epithelioid type glioblastoma harboring BRAF V600E, although the patient soon passed due to complications (PMID: 31386052). | 31386052 |
| BRAF V600E | glioblastoma | predicted - sensitive | RAF Inhibitor (Pan) | Vemurafenib | Case Reports/Case Series | Actionable | In a clinical case study, Zelboraf (vemurafenib) treatment resulted in tumor regression as confirmed by MRI after 3-weeks of treatment in a patient with epithelioid glioblastoma harboring BRAF V600E (PMID: 31217909). | 31217909 |
| BRAF V600E | colorectal cancer | sensitive | Lapatinib + Panobinostat | Preclinical | Actionable | In a preclinical study, Tykerb (lapatinib) and Faridak (panobinostat) worked synergistically to inhibit growth of BRAF V600E mutant colorectal cancer cells in culture (PMID: 21464044). | 21464044 | |
| BRAF V600E | melanoma | sensitive | BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib + Encorafenib | FDA approved - On Companion Diagnostic | Actionable | In a Phase III (COLUMBUS) trial that supported FDA approval, Braftovi (encorafenib) in combination with Mektovi (binimetinib) resulted in a median overall survival (OS) of 33.6 months, a 1-year OS rate of 77.5%, and a 2-year OS rate of 57.7% in patients with advanced melanoma harboring BRAF V600E/K mutations compared to a median OS of 16.9 months and 1- and 2-year OS rates of 63.1% and 43.2%, respectively, in the Zelboraf (vemurafenib) treated group (PMID: 30219628; NCT01909453). | detail... 30219628 detail... detail... |
| BRAF V600E | melanoma | sensitive | BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib + Encorafenib | FDA approved - On Companion Diagnostic | Actionable | In a Phase III (COLUMBUS) trial that supported FDA approval, Braftovi (encorafenib) in combination with Mektovi (binimetinib) demonstrated improved tolerability profile and efficacy, resulted in a progression-free survival of 14.9 months in patients with advanced melanoma harboring BRAF V600E/K mutations, comparing to 7.3 months in the Zelboraf (vemurafenib) group (HR=0.54, p<0.0001) (PMID: 29573941; NCT01909453), and both BRAF V600E and V600K are on the companion diagnostic. | 29573941 detail... detail... detail... |
| BRAF V600E | Advanced Solid Tumor | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | CI-1040 | Preclinical | Actionable | In a preclinical study, CI-1040 (PD184352) inhibited Erk phosphorylation and growth of transformed cells expressing BRAF V600E in culture (PMID: 20538618). | 20538618 |
| BRAF V600E | melanoma | sensitive | RAF Inhibitor (Pan) | AZ628 | Preclinical - Cell culture | Actionable | In a preclinical study, AZ628 inhibited proliferation of melanoma cell lines harboring either monomeric BRAF V600E or dimeric isoform of V600E which conferred Zelboraf (vemurafenib)-resistance in culture (PMID: 27523909). | 27523909 |
| BRAF V600E | thyroid gland cancer | sensitive | Dasatinib + SCH772984 | Preclinical - Cell culture | Actionable | In a preclinical study, Sprycel (dasatinib) and SCH772984 synergistically inhibited proliferation and induced apoptosis in both parental thyroid cancer cell lines harboring BRAF V600E and those acquired Sprycel (dasatinib)-resistance in culture (PMID: 27222538). | 27222538 | |
| BRAF V600E | rectum cancer | resistant | Panitumumab | Guideline | Actionable | Vectibix (panitumumab), as a monotherapy, is not indicated for use in rectum cancer patients with BRAF V600E (NCCN.org). | detail... | |
| BRAF V600E | thyroid gland cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dasatinib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Sprycel (dasatinib) and Mekinist (trametinib) synergistically inhibited proliferation and induced apoptosis in both parental thyroid cancer cell lines harboring BRAF V600E and those acquired Sprycel (dasatinib)-resistance in culture (PMID: 27222538). | 27222538 |
| BRAF V600E | melanoma | sensitive | RAF Inhibitor (Pan) | BGB659 | Preclinical - Cell culture | Actionable | In a preclinical study, BGB659 treatment inhibited Erk phosphorylation and reduced proliferation of a melanoma cells harboring either monomeric BRAF V600E or dimeric isoform (p61) of V600E in culture (PMID: 30559419). | 30559419 |
| BRAF V600E | neuroendocrine carcinoma | predicted - sensitive | RAF Inhibitor (Pan) | Vemurafenib | Case Reports/Case Series | Actionable | In a Phase II trial (VE-BASKET), responses were seen in patients with neuroendocrine carcinoma harboring BRAF V600E (n=3) when treated with Zelboraf (vemurafenib), including 1 patient with a partial response (PMID: 32029534; NCT01524978). | 32029534 |
| BRAF V600E | melanoma | sensitive | KRT-232 + Navitoclax | Preclinical - Pdx | Actionable | In a preclinical study, the combination of KRT-232 (AMG 232) and Navitoclax (ABT-263) resulted in a greater response than either drug alone in patient-derived xenograft (PDX) models of melanoma harboring BRAF V600E, leading to tumor regression (PMID: 32234759). | 32234759 | |
| BRAF V600E | anaplastic pleomorphic xanthoastrocytoma | predicted - sensitive | BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, Mekinist (trametinib) and Tafinlar (dabrafenib) combination treatment resulted in an ongoing partial response 8 months after initiation of treatment in a patient with anaplastic pleomorphic xanthoastrocytoma harboring BRAF V600E, and a near complete response after 3 months of treatment in another patient with relapsed disease (PMID: 28984141). | 28984141 |
| BRAF V600E | colorectal cancer | sensitive | BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | BI 882370 + Trametinib | Preclinical | Actionable | In a preclinical study, colorectal cancer cells harboring BRAF V600E were sensitive to the combination of BI 882370 and Mekinist (trametinib) in xenograft models, resulting in tumor growth inhibition and partial tumor regression (PMID: 26916115). | 26916115 |
| BRAF V600E | low grade glioma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor RAF Inhibitor (Pan) | Cobimetinib + Vemurafenib | Guideline | Actionable | Combination of Zelboraf (vemurafenib) and Cotellic (cobimetinib) is included in guidelines for patients with recurrent or progressive low grade glioma harboring BRAF V600E (NCCN.org). | detail... |
| BRAF V600E | melanoma | conflicting | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | PD-0325901 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, a melanoma cell line xenograft model harboring BRAF V600E treated with PD-0325901 demonstrated stable tumor growth, but by day 44, growth ensued and thus, demonstrated no benefit (PMID: 27488531). | 27488531 |
| BRAF V600E | melanoma | conflicting | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | PD-0325901 | Preclinical - Cell culture | Actionable | In a preclinical study, PD-0325901 inhibited growth of melanoma cell lines harboring BRAF V600E in culture (PMID: 26267534). | 26267534 |
| BRAF V600E | colon cancer | sensitive | Gedatolisib | Preclinical | Actionable | In a preclinical study, Gedatolisib (PKI-587) inhibited Braf V600E in vitro and inhibited growth of human colon cancer cells harboring BRAF V600E in culture (PMID: 21325073, PMID: 24042735). | 24042735 21325073 | |
| BRAF V600E | peritoneal serous papillary adenocarcinoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Case Reports/Case Series | Actionable | In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment resulted in an objective response rate of 37.9% (11/29) in patients with advanced solid tumors harboring BRAF V600E, 1 patient with mucinous-papillary serous adenocarcinoma of the peritoneum achieved a partial response (PMID: 32758030; NCT02465060). | 32758030 |
| BRAF V600E | colon carcinoma | sensitive | BRAF Inhibitor | RXDX-105 | Preclinical - Cell line xenograft | Actionable | In preclinical studies, CEP-32496 (RXDX-105) reduced tumor volume and promoted tumor regression in xenograft models of a BRAF V600E mutant human colon carcinoma cell line (PMID: 22319199). | 22319199 |
| BRAF V600E | melanoma | sensitive | Saracatinib | Preclinical | Actionable | In a preclinical study, saracatinib inhibited proliferation of human melanoma cell lines harboring BRAF V600E that are resistant to Braf inhibition in culture (PMID: 23242808). | 23242808 | |
| BRAF V600E | melanoma | sensitive | BRAF Inhibitor | Encorafenib + Ribociclib | Phase Ib/II | Actionable | In a Phase Ib/II trial, Encorafenib (LGX818) and Kisqali (ribociclib) combination treatment resulted in confirmed partial response in 7.1% (2/28), unconfirmed partial response in 10.7% (3/28), and stable disease in 35.7% (10/28) of patients with melanoma harboring BRAF V600E (PMID: 28351928). | 28351928 |
| BRAF V600E | colon cancer | sensitive | RAF Inhibitor (Pan) | Navitoclax + Vemurafenib | Preclinical | Actionable | In a preclinical study, Navitoclax (ABT-263) enhanced the inhibitory effect of Zelboraf (vemurafenib) on human colon cancer cells harboring BRAF V600E in culture (PMID: 25665005). | 25665005 |
| BRAF V600E | lung non-small cell carcinoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Navitoclax + Trametinib | Preclinical | Actionable | In a preclinical study, Navitoclax (ABT-263) enhanced the inhibitory effect of Mekinist (trametinib) on human non-small cell lung cancer cells harboring BRAF V600E in culture (PMID: 25665005). | 25665005 |
| BRAF V600E | ganglioglioma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor RAF Inhibitor (Pan) | Cobimetinib + Vemurafenib | Guideline | Actionable | Zelboraf (vemurafenib) and Cotellic (cobimetinib) combination therapy is included in guidelines as an adjuvant treatment for patients with ganglioglioma harboring BRAF V600E (NCCN.org). | detail... |
| BRAF V600E | colorectal cancer | sensitive | SCH772984 | Preclinical | Actionable | In a preclinical study, SCH772984 inhibited growth of colorectal cancer cell lines harboring BRAF V600E in culture (PMID: 26267534). | 26267534 | |
| BRAF V600E | colorectal cancer | sensitive | BRAF Inhibitor | Cetuximab + Dabrafenib | Preclinical - Cell culture | Actionable | In a preclinical study, combination therapy consisting of Erbitux (cetuximab) and Tafinlar (dabrafenib) inhibited survival of colorectal cancer cell lines harboring BRAF V600E in culture (PMID: 27312529). | 27312529 |
| BRAF V600E | melanoma | decreased response | Pembrolizumab | Clinical Study | Actionable | In a retrospective analysis, patients with melanoma harboring BRAF V600E (n=84) had decreased response rates (29% vs. 53%, p=0.059), progression-free survival (2.7 vs. 19 months, p=0.049), and overall survival (11.7 vs. 20.4 months, p=0.081) relative to patients with BRAF V600K (n=19) when treated with Keytruda (pembrolizumab) (n=62 and 17 for BRAF V600E and V600K, respectively) or Opdivo (nivolumab) (n=22 and 2 for BRAF V600E and V600K, respectively) (PMID: 30630828). | 30630828 | |
| BRAF V600E | high grade glioma | predicted - sensitive | RAF Inhibitor (Pan) | Vemurafenib | Phase II | Actionable | In a Phase II trial (VE-BASKET), Zelboraf (vemurafenib) treatment resulted in an objective response rate of 25% (6/24, 1 complete response, 5 partial responses) in patients with gliomas harboring BRAF V600E, with a median progression free survival of 5.5-months, a median overall survival of 28.2 months (PMID: 30351999; NCT01524978). | 30351999 |
| BRAF V600E | high grade glioma | predicted - sensitive | RAF Inhibitor (Pan) | Vemurafenib | Case Reports/Case Series | Actionable | In a Phase II trial (VE-BASKET), responses were seen in glioma patients harboring BRAF V600E (n=24) when treated with Zelboraf (vemurafenib), including 1 patient with a complete response and 5 patients with a partial response (PMID: 32029534; NCT01524978). | 32029534 |
| BRAF V600E | anaplastic astrocytoma | predicted - sensitive | RAF Inhibitor (Pan) | Vemurafenib | Case Reports/Case Series | Actionable | In a Phase II trial (VE-BASKET), Zelboraf (vemurafenib) treatment resulted in a partial response in 1 of 5 patients with anaplastic astrrocytoma harboring BRAF V600E, with 2 other patients achieved stable disease lasting 14.9, and 5.6 months, respectively (PMID: 30351999; NCT01524978). | 30351999 |
| BRAF V600E | colorectal cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Cetuximab + Selumetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Koselugo (selumetinib) and Erbitux (cetuximab) combination treatment inhibited survival of colorectal cancer cell lines harboring BRAF V600E in culture (PMID: 27312529). | 27312529 |
| BRAF V600E | thyroid gland carcinoma | predicted - sensitive | BRAF Inhibitor | Dabrafenib | Case Reports/Case Series | Actionable | In a Phase I trial, Tafinlar (dabrafenib) treatment resulted in a partial response in 29% (4/14) and stable disease in 43% (6/14) of patients with thyroid carcinoma harboring BRAF V600E, with 64% (9/14) of patients achieved at least a 10% decrease by RECIST, and a median progression-free survival of 11.3 months among responders (PMID: 25285888; NCT00880321). | 25285888 |
| BRAF V600E | pilocytic astrocytoma | predicted - sensitive | RAF Inhibitor (Pan) | Vemurafenib | Case Reports/Case Series | Actionable | In a Phase II trial (VE-BASKET), Zelboraf (vemurafenib) treatment resulted in a partial response in a patient with pilocytic astrrocytoma harboring BRAF V600E who stayed on treatment for 15.3 months (PMID: 30351999; NCT01524978). | 30351999 |
| BRAF V600E | thyroid gland follicular carcinoma | sensitive | BRAF Inhibitor | Dabrafenib | Guideline | Actionable | Tafinlar (dabrafenib) is included in guidelines for patients with recurrent, advanced, or metastatic thyroid follicular carcinoma harboring BRAF V600E for whom clinical trials are not available or appropriate (NCCN.org). | detail... |
| BRAF V600E | colon cancer | sensitive | BRAF Inhibitor | Cetuximab + Encorafenib | Guideline | Actionable | Braftovi (encorafenib) in combination with Erbitux (cetuximab) is included in guidelines as primary or subsequent therapy for patients with colon cancer harboring BRAF V600E (NCCN.org). | detail... |
| BRAF V600E | anaplastic astrocytoma | sensitive | BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Guideline | Actionable | Combination of Mekinist (trametinib) and Tafinlar (dabrafenib) is included in guidelines for patients with recurrent anaplastic gliomas harboring BRAF V600E, including anaplastic astrocytoma (NCCN.org). | detail... |
| BRAF V600E | thyroid gland cancer | sensitive | BRAF Inhibitor | PLX4720 + Ponatinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Iclusig (ponatinib) and PLX4720 treatment demonstrated synergy, and inhibited Erk, Mek, and c-jun phosphorylation, reduced cell proliferation, colony formation, and migration, and induced apoptosis in thyroid cancer cells harboring BRAF V600E and in PLX4720-resistant cells harboring BRAF V600E in culture, and inhibited tumor growth, reduced lung and liver metastases, and increased survival in cell line xenograft models (PMID: 31937621). | 31937621 |
| BRAF V600E | glioblastoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor RAF Inhibitor (Pan) | Cobimetinib + Vemurafenib | Guideline | Actionable | Combination of Zelboraf (vemurafenib) and Cotellic (cobimetinib) is included in guidelines for patients with recurrent glioblastoma harboring BRAF V600E (NCCN.org). | detail... |
| BRAF V600E | glioblastoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor RAF Inhibitor (Pan) | Cobimetinib + Vemurafenib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with epithelioid glioblastoma harboring BRAF V600E continued to response as Cotellic (cobimetinib) was added to Zelboraf (vemurafenib) treatment (PMID: 31217909). | 31217909 |
| BRAF V600E | skin melanoma | no benefit | YM-254890 | Preclinical - Cell culture | Actionable | In a preclinical study, YM-254890 treatment did not inhibit cell viability of a cutaneous melanoma cell line harboring BRAF V300E in culture (PMID: 33229459). | 33229459 | |
| BRAF V600E | thyroid gland cancer | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of both parental thyroid cancer cell lines harboring BRAF V600E and those acquired Sprycel (dasatinib)-resistance in culture (PMID: 27222538). | 27222538 |
| BRAF V600E | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | FDA approved - On Companion Diagnostic | Actionable | In a Phase III trial (METRIC) that supported FDA approval, Mekinist (trametinib) treatment, as compared to Deticine (dacarbazine) or Taxol (paclitaxel) treatment, resulted in improved progression-free survival of 4.8 months versus 1.5 months and an overall six month survival rate of 81% versus 67% in patients with BRAF V600E/K-positive metastatic melanoma (PMID: 22663011; NCT01245062). | 22663011 detail... detail... |
| BRAF V600E | colorectal cancer | sensitive | BRAF Inhibitor | Alpelisib + Cetuximab + Encorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, combination therapy consisting of Erbitux (cetuximab), Encorafenib (LGX818) and Alpelisib (BYL719) inhibited survival of colorectal cancer cell lines harboring BRAF V600E in culture (PMID: 27312529). | 27312529 |
| BRAF V600E | colorectal cancer | sensitive | DT01 + Fluorouracil + Oxaliplatin | Preclinical - Cell line xenograft | Actionable | In a preclinical study, DT01 increased sensitivity of human colorectal cancer (CRC) cells harboring BRAF V600E to Eloxatin (oxaliplatin) and Adrucil (5-fluorouracil), and the combination resulted in decreased liver tumor growth in CRC cell line xenograft metastasis models (PMID: 26637369). | 26637369 | |
| BRAF V600E | melanoma | sensitive | ERAS-007 | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, ERAS-007 (ASN007) treatment inhibited proliferation and Erk signaling in a melanoma cell line harboring BRAF V600E in culture, and inhibited tumor growth in patient-derived xenograft (PDX) models, including a Zelboraf (vemurafenib)-resistant PDX model (PMID: 34337566). | 34337566 | |
| BRAF V600E | colorectal cancer | sensitive | RAF Inhibitor (Pan) | Irinotecan + Vemurafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Zelboraf (vemurafenib) treatment in combination with Camptosar (irinotecan) enhanced tumor growth inhibition and increased survival in a cell line xenograft model of colorectal cancer harboring BRAF V600E (PMID: 22180495). | 22180495 |
| BRAF V600E | ovarian serous carcinoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Case Reports/Case Series | Actionable | In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment resulted in an objective response rate of 37.9% (11/29) in patients with advanced solid tumors harboring BRAF V600E, of 5 patients with low grade serous ovarian carcinoma, 4 achieved a partial response (PR), 1 had stable disease, 3 of the PRs lasted over 12 months (PMID: 32758030; NCT02465060). | 32758030 |
| BRAF V600E | melanoma | sensitive | GSK2126458 | Preclinical | Actionable | In a preclinical study, Omipalisib (GSK2126458) inhibited the growth of melanoma cell lines harboring BRAF V600E in culture (PMID: 22389471). | 22389471 | |
| BRAF V600E | melanoma | sensitive | BRAF Inhibitor | SB590885 | Preclinical - Cell culture | Actionable | In a preclinical study, SB590885 inhibited proliferation of melanoma cell lines harboring either monomeric BRAF V600E or dimeric isoform of V600E which conferred Zelboraf (vemurafenib)-resistance in culture (PMID: 27523909). | 27523909 |
| BRAF V600E | colon cancer | sensitive | BRAF Inhibitor | Encorafenib + Panitumumab | Guideline | Actionable | Braftovi (encorafenib) in combination with Vectibix (panitumumab) is included in guidelines as primary or subsequent therapy for patients with colon cancer harboring BRAF V600E (NCCN.org). | detail... |
| BRAF V600E | colon cancer | predicted - sensitive | RAF Inhibitor (Pan) | Cetuximab + Sorafenib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with metastatic colon cancer harboring BRAF V600E demonstrated mixed radiographic response with slight progression in some locations and stable disease in other locations for 7 months following treatment with the combination of Nexavar (sorafenib) and Erbitux (cetuximab) (PMID: 23792568). | 23792568 |
| BRAF V600E | lung carcinoma | resistant | Dasatinib | Preclinical | Actionable | In a preclinical study, Sprycel (dasatinib) failed to induce apoptosis in lung carcinoma cells expressing BRAF V600E (PMID: 22649091). | 22649091 | |
| BRAF V600E | colorectal cancer | sensitive | BRAF Inhibitor | BI 882370 + Cetuximab | Preclinical | Actionable | In a preclinical study, colorectal cancer cells harboring BRAF V600E were sensitive to the combination of BI 882370 and Erbitux (cetuximab) in xenograft models, resulting in tumor growth inhibition and partial tumor regression (PMID: 26916115). | 26916115 |
| BRAF V600E | high grade glioma | predicted - sensitive | RAF Inhibitor (Pan) | LY3009120 | Preclinical - Patient cell culture | Actionable | In a preclinical study, LY3009120 treatment led to inhibition of cell viability and growth in a patient-derived glioma cell line harboring BRAF V600E in culture (PMID: 34433654). | 34433654 |
| BRAF V600E | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Ganetespib + TAK-733 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the Hsp90 inhibitor, Ganetespib, in combination with the MEK1/2 inhibitor TAK-733, caused the regression of tumors in vemurafenib-resistant cell line xenograft models of melanoma (PMID: 24398428). | 24398428 |
| BRAF V600E | colorectal cancer | sensitive | BRAF Inhibitor | Dabrafenib + Panitumumab | Phase I | Actionable | In a Phase I trial, combination therapy consisting of Tafinlar (dabrafenib) and Vectibix (panitumumab) resulted in an overall response rate of 10% (2/20, 1 complete response, 1 partial response), stable disease in 80% (16/20), and a median progression-free survival of 3.5 months in patients with BRAF V600E colorectal cancer (PMID: 29431699; NCT01750918). | 29431699 |
| BRAF V600E | colorectal cancer | sensitive | BRAF Inhibitor | Dabrafenib + Panitumumab | Phase Ib/II | Actionable | In a Phase Ib/II trial, treatment with the combination of Vectibix (panitumumab) and Tafinlar (dabrafenib) resulted in stable disease in 7/8 colorectal cancer patients harboring a BRAF V600E mutation (J Clin Oncol 32:5s, 2014 (suppl; abstr 3515)). | detail... |
| Clinical Trial | Phase | Therapies | Title | Recruitment Status | Covered Countries | Other Countries |
|---|---|---|---|---|---|---|
| NCT04655976 | Phase II | Docetaxel Docetaxel + Dostarlimab-gxly + TSR-022 Docetaxel + Dostarlimab-gxly | Study of Cobolimab in Combination With Dostarlimab and Docetaxel in Advanced NSCLC Participants (COSTAR Lung) | Recruiting | USA | CAN | 11 |
| NCT04576117 | Phase III | Selumetinib Selumetinib + Vinblastine | A Study to Compare Treatment With the Drug Selumetinib Alone Versus Selumetinib and Vinblastine in Patients With Recurrent or Progressive Low-Grade Glioma | Recruiting | USA | 0 |
| NCT03709706 | Phase Ib/II | NY-ESO-1-c259T + Pembrolizumab NY-ESO-1-c259T | Pilot Immunotherapy Study With Autologous T-cells Specific for NY-ESO-1/ LAGE-1a-positive Advanced NSCLC Either Alone or in Combination With Pembrolizumab | Active, not recruiting | USA | CAN | 3 |
| NCT04310397 | Phase II | Dabrafenib + Trametinib Dabrafenib + Spartalizumab + Trametinib | Dabrafenib, Trametinib, and Spartalizumab for the Treatment of BRAF V600E or V600K Mutation Positive Stage IIIB/C/D Melanoma | Active, not recruiting | USA | 0 |
| NCT01336634 | Phase II | Dabrafenib Dabrafenib + Trametinib | Study of Selective BRAF Kinase Inhibitor Dabrafenib Monotherapy Twice Daily and in Combination With Dabrafenib Twice Daily and Trametinib Once Daily in Combination Therapy in Subjects With BRAF V600E Mutation Positive Metastatic (Stage IV) Non-small Cell Lung Cancer. | Completed | USA | 10 |
| NCT02949843 | Phase II | Nivolumab + Pembrolizumab | Targeted Therapy in Treating Patients With Incurable Non-Small Cell Lung Cancer With Genetic Mutations | Terminated | USA | 0 |
| NCT03864042 | Phase I | Caffeine + Dextromethorphan + Losartan + Midazolam + Omeprazole Modafinil Bupropion + Rosuvastatin Binimetinib + Encorafenib | Pharmacokinetic Drug-drug Interaction Study of Encorafenib and Binimetinib on Probe Drugs in Patients With BRAF V600-mutant Melanoma or Other Advanced Solid Tumors | Recruiting | USA | CAN | 3 |
| NCT01754376 | Phase II | Aldesleukin + Vemurafenib | Combined BRAF-Targeted Therapy and Immunotherapy for Melanoma | Terminated | USA | 0 |
| NCT01897116 | Phase I | Hydroxychloroquine + Vemurafenib | A Phase I Trial of Vemurafenib and Hydroxychloroquine in Patients With Advanced BRAF Mutant Melanoma | Completed | USA | 0 |
| NCT04759846 | Phase I | Binimetinib + Encorafenib | Hepatic Impairment Study of Encorafenib in Combination With Binimetinib in BRAF Melanoma | Not yet recruiting | 3 | |
| NCT03668431 | Phase II | Dabrafenib + Spartalizumab + Trametinib | Dabrafenib + Trametinib + PDR001 In Colorectal Cancer | Recruiting | USA | 0 |
| NCT03973918 | Phase II | Binimetinib + Encorafenib | Study of Binimetinib With Encorafenib in Adults With Recurrent BRAF V600-Mutated HGG (BRAF) | Recruiting | USA | 0 |
| NCT03475004 | Phase II | Bevacizumab + Binimetinib + Pembrolizumab | Study of Pembrolizumab, Binimetinib, and Bevacizumab in Patients With Refractory Colorectal Cancer | Recruiting | USA | 0 |
| NCT02065063 | Phase I | Palbociclib + Trametinib | A Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics, and Anti-Cancer Activity of Trametinib in Combination With Palbociclib in Subjects With Solid Tumors | Completed | USA | 0 |
| NCT01638676 | Phase Ib/II | Metformin + Vemurafenib | A Phase I/II Trial of Vemurafenib and Metformin to Melanoma Patients | Recruiting | USA | 0 |
| NCT03693170 | Phase II | Binimetinib + Cetuximab + Encorafenib | Encorafenib, Binimetinib and Cetuximab in Subjects With Previously Untreated BRAF-mutant ColoRectal Cancer (ANCHOR-CRC) | Active, not recruiting | USA | 8 |
| NCT05039177 | Phase Ib/II | Cetuximab + Encorafenib + ERAS-007 ERAS-007 + Palbociclib | A Study of ERAS-007 in Patients With Advanced Gastrointestinal Malignancies (HERKULES-3) | Recruiting | USA | 0 |
| NCT03708328 | Phase I | RO7121661 | A Dose Escalation and Expansion Study of RO7121661, a PD-1/TIM-3 Bispecific Antibody, in Participants With Advanced and/or Metastatic Solid Tumors | Active, not recruiting | USA | 5 |
| NCT01711632 | Phase II | Vemurafenib | BRAF Inhibitor, Vemurafenib, in Patients With Relapsed or Refractory Hairy Cell Leukemia | Active, not recruiting | USA | 0 |
| NCT01659151 | Phase II | Aldesleukin Fludarabine Vemurafenib | Vemurafenib With Lymphodepletion Plus Adoptive Cell Transfer and High Dose IL-2 Metastatic Melanoma | Active, not recruiting | USA | 0 |
| NCT04044430 | Phase Ib/II | Binimetinib + Encorafenib + Nivolumab | Encorafenib, Binimetinib, and Nivolumab in Treating Patients With Microsatellite Stable BRAF V600E Metastatic Colorectal Cancer | Active, not recruiting | USA | 0 |
| NCT03520686 | Phase III | ALT-803 + Carboplatin + Pembrolizumab + Pemetrexed Disodium ALT-803 + Cisplatin + Pembrolizumab + Pemetrexed Disodium Pembrolizumab Carboplatin + Paclitaxel + Pembrolizumab Carboplatin + Nab-paclitaxel + Pembrolizumab ALT-803 + Pembrolizumab Carboplatin + Pembrolizumab + Pemetrexed Disodium Cisplatin + Pembrolizumab + Pemetrexed Disodium ALT-803 + Carboplatin + Nab-paclitaxel + Pembrolizumab | QUILT 2.023: A Study of N-803 in Combination With Current Standard of Care vs Standard of Care as First-Line Treatment for Patients With Stage 3 or 4 NSCLC. | Recruiting | USA | 0 |
| NCT04534283 | Phase II | Abemaciclib + LY3214996 | A Basket Trial of an ERK1/2 Inhibitor (LY3214996) in Combination With Abemaciclib. | Recruiting | USA | 0 |
| NCT04581824 | Phase II | Carboplatin + Pembrolizumab + Pemetrexed Disodium Cisplatin + Pembrolizumab + Pemetrexed Disodium Cisplatin + Dostarlimab-gxly + Pemetrexed Disodium Carboplatin + Dostarlimab-gxly + Pemetrexed Disodium | Efficacy Comparison of Dostarlimab Plus Chemotherapy Versus Pembrolizumab Plus Chemotherapy in Participants With Metastatic Non-squamous Non-small Cell Lung Cancer (NSCLC) | Recruiting | USA | 10 |
| NCT02257424 | Phase Ib/II | Dabrafenib + Hydroxychloroquine + Trametinib | Dabrafenib, Trametinib and Hydroxychloroquine in Patients With Advanced BRAF Mutant Melanoma (BAMM) | Completed | USA | 0 |
| NCT02367859 | Phase II | Dabrafenib + Trametinib | Dabrafenib and Trametinib in Treating Patients With BRAF Mutated Ameloblastoma | Completed | USA | 0 |
| NCT04034459 | Phase II | Bevacizumab + Fluorouracil + Irinotecan + Leucovorin + Oxaliplatin Cetuximab + Fluorouracil + Irinotecan + Leucovorin + Oxaliplatin | FOLFOXIRI Plus Cetuximab vs. FOLFOXIRI Plus Bevacizumab 1st-line in BRAF-mutated mCRC (AIO-KRK-0116) | Active, not recruiting | 1 | |
| NCT04238624 | Phase II | Cemiplimab + Dabrafenib + Trametinib | Study of Cemiplimab Combined With Dabrafenib and Trametinib in People With Anaplastic Thyroid Cancer | Recruiting | USA | 0 |
| NCT03631706 | Phase II | M7824 Pembrolizumab | M7824 Versus Pembrolizumab as a First-line (1L) Treatment in Participants With Programmed Death-ligand 1 (PD-L1) Expressing Advanced Non-small Cell Lung Cancer (NSCLC) | Active, not recruiting | USA | CAN | 16 |
| NCT02164916 | Phase II | Cetuximab + Irinotecan Cetuximab + Irinotecan + Vemurafenib | S1406 Phase II Study of Irinotecan and Cetuximab With or Without Vemurafenib in BRAF Mutant Metastatic Colorectal Cancer | Completed | USA | 0 |
| NCT03138889 | Phase I | NKTR-214 + Pembrolizumab | A Study of a CD122-Biased Cytokine (NKTR-214) in Combination With Anti-PD-1 (Pembrolizumab) in Patients With Select Advanced or Metastatic Solid Tumors (PROPEL) | Recruiting | USA | 5 |
| NCT01089101 | Phase Ib/II | Selumetinib | Selumetinib in Treating Young Patients With Recurrent or Refractory Low Grade Glioma | Active, not recruiting | USA | 0 |
| NCT03365882 | Phase II | Cetuximab + Irinotecan Pertuzumab + Trastuzumab | S1613, Trastuzumab and Pertuzumab or Cetuximab and Irinotecan Hydrochloride in Treating Patients With Locally Advanced or Metastatic HER2/Neu Amplified Colorectal Cancer That Cannot Be Removed by Surgery | Recruiting | USA | 1 |
| NCT03255083 | Phase I | DS-1205c + Osimertinib | DS-1205c With Osimertinib for Metastatic or Unresectable Epidermal Growth Factor Receptor (EGFR)-Mutant Non-Small Cell Lung Cancer | Terminated | 1 | |
| NCT04418167 | Phase I | JSI-1187 Dabrafenib + JSI-1187 | JSI-1187-01 Monotherapy and in Combination With Dabrafenib for Advanced Solid Tumors With MAPK Pathway Mutations | Recruiting | USA | 0 |
| NCT02014909 | Phase I | CDX-3379 CDX-3379 + Vemurafenib CDX-3379 + Trastuzumab CDX-3379 + Cetuximab CDX-3379 + Erlotinib | A Phase 1 Study to Evaluate the Safety and Pharmacokinetics of KTN3379 in Adult Subjects With Advanced Tumors | Completed | USA | 0 |
| NCT01709292 | Phase II | Vemurafenib | Vemurafenib Neoadjuvant Trial in Locally Advanced Thyroid Cancer | Active, not recruiting | USA | 0 |
| NCT04201457 | Phase Ib/II | Hydroxychloroquine + Trametinib Dabrafenib + Hydroxychloroquine + Trametinib | A Trial of Dabrafenib, Trametinib and Hydroxychloroquine for Patients With Recurrent LGG or HGG With a BRAF Aberration | Recruiting | USA | 0 |
| NCT04862780 | Phase Ib/II | BLU-945 | Study Targeting EGFR Resistance Mechanisms in NSCLC | Recruiting | USA | 3 |
| NCT04557956 | Phase Ib/II | Tazemetostat Dabrafenib + Tazemetostat + Trametinib | Testing the Addition of the Anti-cancer Drug, Tazemetostat, to the Usual Treatment (Dabrafenib and Trametinib) for Metastatic Melanoma That Has Progressed on the Usual Treatment | Recruiting | USA | 0 |
| NCT04800822 | Phase I | PF-07284892 Cetuximab + Encorafenib + PF-07284892 Lorlatinib + PF-07284892 Binimetinib + PF-07284892 | PF-07284892 in Participants With Advanced Solid Tumors | Recruiting | USA | 0 |
| NCT04074096 | Phase II | Binimetinib + Encorafenib + Pembrolizumab | Binimetinib Encorafenib Pembrolizumab +/- Stereotactic Radiosurgery in BRAFV600 Melanoma With Brain Metastasis (BEPCOME-MB) | Not yet recruiting | 1 | |
| NCT04551521 | Phase II | Atezolizumab Atezolizumab + Ipatasertib Atezolizumab + Pertuzumab + Trastuzumab Atezolizumab + Cobimetinib Alectinib Atezolizumab + Cobimetinib + Vemurafenib | CRAFT: The NCT-PMO-1602 Phase II Trial | Recruiting | 1 | |
| NCT01721603 | Phase II | Dabrafenib | A Phase 2 Prospective Trial of Dabrafenib With Stereotactic Radiosurgery in BRAFV600E Melanoma Brain Metastases | Terminated | USA | 0 |
| NCT03235245 | Phase II | Binimetinib + Encorafenib Ipilimumab + Nivolumab | Immunotherapy With Ipilimumab and Nivolumab Preceded or Not by a Targeted Therapy With Encorafenib and Binimetinib (EBIN) | Recruiting | 8 | |
| NCT04995523 | Phase Ib/II | AZD2936 | A Study to Assess the Safety and Efficacy of AZD2936 in Participants With Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC) (ARTEMIDE-01) | Recruiting | 6 | |
| NCT04061980 | Phase II | Binimetinib + Encorafenib Binimetinib + Encorafenib + Nivolumab | Encorafenib and Binimetinib With or Without Nivolumab in Treating Patients With Metastatic Radioiodine Refractory BRAF V600 Mutant Thyroid Cancer | Recruiting | USA | 0 |
| NCT01750918 | Phase II | Fluorouracil Dabrafenib + Panitumumab Dabrafenib + Panitumumab + Trametinib Panitumumab + Trametinib | BRAF/MEK/EGFR Inhibitor Combination Study in Colorectal Cancer (CRC) | Completed | USA | 7 |
| NCT04675710 | Phase II | Dabrafenib + Pembrolizumab + Trametinib | Pembrolizumab, Dabrafenib, and Trametinib Before Surgery for the Treatment of BRAF-Mutated Anaplastic Thyroid Cancer | Recruiting | USA | 0 |
| NCT03608046 | Phase II | Avelumab + Cetuximab + Irinotecan | Avelumab Combined With Cetuximab and Irinotecan for Treatment Refractory Metastatic Colorectal Microsatellite Stable Cancer (AVETUXIRI) | Recruiting | 1 | |
| NCT02693535 | Phase II | Cobimetinib + Vemurafenib Regorafenib Ipilimumab + Nivolumab Palbociclib Afatinib Talazoparib Pembrolizumab Temsirolimus Pertuzumab + Trastuzumab Crizotinib Abemaciclib Sunitinib Olaparib | TAPUR: Testing the Use of Food and Drug Administration (FDA) Approved Drugs That Target a Specific Abnormality in a Tumor Gene in People With Advanced Stage Cancer | Recruiting | USA | 0 |
| NCT03840915 | Phase Ib/II | Cisplatin + M7824 + Pemetrexed Disodium Docetaxel + M7824 Carboplatin + M7824 + Pemetrexed Disodium Cisplatin + Gemcitabine + M7824 Carboplatin + Gemcitabine + M7824 Carboplatin + M7824 + Nab-paclitaxel | M7824 in Combination With Chemotherapy in Stage IV Non-small Cell Lung Cancer (NSCLC) | Active, not recruiting | USA | 2 |
| NCT05048797 | Phase III | Cisplatin + Pembrolizumab + Pemetrexed Disodium Carboplatin + Pembrolizumab + Pemetrexed Disodium Trastuzumab deruxtecan | A Study to Investigate the Efficacy and Safety of Trastuzumab Deruxtecan as the First Treatment Option for Unresectable, Locally Advanced/Metastatic Non-Small Cell Lung Cancer With HER2 Mutations | Recruiting | USA | 17 |
| NCT01534897 | Phase I | Dabrafenib | Re-differentiation of Radioiodine-Refractory BRAF V600E-mutant Papillary Thyroid Carcinoma With GSK2118436 | Completed | USA | 0 |
| NCT04252339 | Phase I | RLY-1971 | RLY-1971 in Subjects With Advanced or Metastatic Solid Tumors | Recruiting | USA | 0 |
| NCT01740648 | Phase I | Fluorouracil + Trametinib | Trametinib, Fluorouracil, and Radiation Therapy Before Surgery in Treating Patients With Stage II-III Rectal Cancer | Active, not recruiting | USA | 0 |
| NCT03975231 | Phase I | Dabrafenib + Trametinib | Dabrafenib, Trametinib, and IMRT in Treating Patients With BRAF Mutated Anaplastic Thyroid Cancer | Recruiting | USA | 0 |
| NCT03224767 | Phase II | Cobimetinib + Vemurafenib | Vemurafenib and Cobimetinib in Treating Patients With BRAF V600E Mutation Positive Craniopharyngioma | Recruiting | USA | 0 |
| NCT03244956 | Phase II | Trametinib Dabrafenib + Trametinib | Efficacy of MEK (Trametinib) and BRAFV600E (Dabrafenib) Inhibitors With Radioactive Iodine (RAI) for the Treatment of Refractory Metastatic Differentiated Thyroid Cancer (MERAIODE) | Active, not recruiting | 1 | |
| NCT04140500 | Phase I | RO7247669 | Dose Escalation Study of a PD1-LAG3 Bispecific Antibody in Patients With Advanced and/or Metastatic Solid Tumors | Recruiting | USA | 7 |
| NCT01726738 | Phase II | Dabrafenib + Trametinib | LCCC 1128: Open Label Phase II Trial of the BRAF Inhibitor (Dabrafenib) and the MEK Inhibitor (Trametinib) in Unresectable Stage III and Stage IV BRAF Mutant Melanoma; Correlation of Resistance With the Kinome and Functional Mutations | Completed | USA | 0 |
| NCT04787341 | Phase II | Regorafenib Panitumumab | PAnitumumab REchallenge Followed by REgorafenib Versus the Reverse Sequence (PARERE) | Recruiting | 1 | |
| NCT04526782 | Phase II | Docetaxel Binimetinib + Encorafenib | ENCOrafenib With Binimetinib in bRAF NSCLC (ENCO-BRAF) | Recruiting | 1 | |
| NCT04117945 | Phase II | Regorafenib Irinotecan + Panitumumab Panitumumab Cetuximab + Irinotecan Cetuximab | Regorafenib, With Cetuximab or Panitumumab, for the Treatment of Unresectable, Locally Advanced, or Metastatic Colorectal Cancer | Recruiting | USA | 0 |
| NCT03732703 | Phase Ib/II | Dexamethasone + Enasidenib + Ixazomib + Pomalidomide Cobimetinib + Dexamethasone + Ixazomib + Pomalidomide Dexamethasone + Erdafitinib + Ixazomib + Pomalidomide Dexamethasone + Ixazomib + Pomalidomide + Venetoclax Abemaciclib + Dexamethasone + Ixazomib + Pomalidomide Daratumumab + Dexamethasone + Ixazomib + Pomalidomide | Myeloma-Developing Regimens Using Genomics (MyDRUG) | Recruiting | USA | 0 |
| NCT03878719 | Phase I | Binimetinib + Encorafenib | Study of the Combination of Binimetinib and Encorafenib in Adolescent Patients With Unresectable or Metastatic BRAF V600-mutant Melanoma | Recruiting | USA | 4 |
| NCT03915951 | Phase II | Binimetinib + Encorafenib | An Open-label Study of Encorafenib + Binimetinib in Patients With BRAFV600E-mutant Non-small Cell Lung Cancer | Recruiting | USA | 4 |
| NCT04126733 | Phase II | Nivolumab + Regorafenib | Study on the Effectiveness and Safety of the Combination of the Two Drugs Regorafenib and Nivolumab in Patients With Colorectal Cancer (Cancer of the Colon or Rectum Classified as Proficient Mismatch Repair and Microsatellite Stable) | Active, not recruiting | USA | 0 |
| NCT02130466 | Phase Ib/II | Dabrafenib + Trametinib Pembrolizumab + Trametinib Dabrafenib + Pembrolizumab Dabrafenib + Pembrolizumab + Trametinib | A Study of the Safety and Efficacy of Pembrolizumab (MK-3475) in Combination With Trametinib and Dabrafenib in Participants With Advanced Melanoma (MK-3475-022/KEYNOTE-022) | Completed | 0 | |
| NCT02928224 | Phase III | Cetuximab + Encorafenib Binimetinib + Cetuximab + Encorafenib Cetuximab + Irinotecan Cetuximab + Fluorouracil + Irinotecan + Leucovorin | Study of Encorafenib + Cetuximab Plus or Minus Binimetinib vs. Irinotecan/Cetuximab or Infusional 5-Fluorouracil (5-FU)/Folinic Acid (FA)/Irinotecan (FOLFIRI)/Cetuximab With a Safety Lead-in of Encorafenib + Binimetinib + Cetuximab in Patients With BRAF V600E-mutant Metastatic Colorectal Cancer (BEACON CRC) | Active, not recruiting | USA | CAN | 25 |
| NCT01748149 | Phase I | Vemurafenib | Vemurafenib in Children With Recurrent/Refractory BRAF Gene V600E (BRAFV600E)-Mutant Gliomas | Active, not recruiting | USA | CAN | 0 |
| NCT04619316 | Phase II | Dabrafenib + Trametinib Trametinib | Enhancing Radioiodine Incorporation Into Radio Iodine Refractory Thyroid Cancers With MAPK Inhibition (ERRITI) | Recruiting | 1 | |
| NCT03181100 | Phase II | Atezolizumab + Cobimetinib Atezolizumab + Bevacizumab Atezolizumab + Nab-paclitaxel Atezolizumab + Cobimetinib + Vemurafenib Atezolizumab + Paclitaxel | Atezolizumab With Chemotherapy in Treating Patients With Anaplastic or Poorly Differentiated Thyroid Cancer | Recruiting | USA | 0 |
| NCT02465060 | Phase II | Erdafitinib Copanlisib Trametinib Crizotinib Sunitinib Sapanisertib Nivolumab AZD4547 Dasatinib Pertuzumab + Trastuzumab Dabrafenib + Trametinib Binimetinib Adavosertib Osimertinib Palbociclib Afatinib Capivasertib Defactinib GSK2636771 Vismodegib Ado-trastuzumab emtansine Larotrectinib Taselisib | Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial) | Recruiting | USA | 2 |
| NCT05026983 | Phase II | Binimetinib + Encorafenib | Binimetinib and Encorafenib for the Treatment of Metastatic Melanoma and Central Nervous System Metastases | Not yet recruiting | USA | 0 |
| NCT03898908 | Phase II | Binimetinib + Encorafenib | Encorafenib and Binimetinib Before Local Treatment in Patients With BRAF Mutant Melanoma Metastatic to the Brain (EBRAIN-MEL) | Recruiting | 1 | |
| NCT03839342 | Phase II | Binimetinib + Encorafenib | Binimetinib and Encorafenib for the Treatment of Advanced Solid Tumors With Non-V600E BRAF Mutations (BEAVER) | Recruiting | CAN | 0 |
| NCT04017650 | Phase Ib/II | Cetuximab + Encorafenib + Nivolumab | Encorafenib, Cetuximab, and Nivolumab in Treating Patients With Microsatellite Stable, BRAFV600E Mutated Unresectable or Metastatic Colorectal Cancer | Recruiting | USA | 0 |
| NCT04585815 | Phase Ib/II | Binimetinib + Encorafenib + PF-06801591 | Umbrella Study of Sasanlimab Combined With Targeted Therapies in Participants With Non Small Cell Lung Cancer | Recruiting | USA | CAN | 2 |
| NCT04657991 | Phase III | Pembrolizumab Binimetinib + Encorafenib + Pembrolizumab | Encorafenib and Binimetinib Plus Pembrolizumab Versus Pembrolizumab for V600E/K Positive Melanoma | Recruiting | USA | 9 |
| NCT03189030 | Phase I | pLADD | Study of Personalized Immunotherapy in Adults With Metastatic Colorectal Cancer | Terminated | USA | 0 |
| NCT02143050 | Phase Ib/II | Dabrafenib + Metformin + Trametinib | Study of Dabrafenib, Trametinib and Metformin for Melanoma Patients | Recruiting | USA | 0 |
| NCT04268550 | Phase II | Selpercatinib | Targeted Treatment for RET Fusion-Positive Advanced Non-Small Cell Lung Cancer (A LUNG-MAP Treatment Trial) | Recruiting | USA | 0 |
| NCT04607421 | Phase III | Bevacizumab + Capecitabine + Oxaliplatin Bevacizumab + Fluorouracil + Leucovorin + Oxaliplatin Cetuximab + Encorafenib Cetuximab + Encorafenib + Fluorouracil + Leucovorin + Oxaliplatin Bevacizumab + Fluorouracil + Irinotecan + Leucovorin + Oxaliplatin Bevacizumab + Fluorouracil + Irinotecan + Leucovorin Cetuximab + Encorafenib + Fluorouracil + Irinotecan + Leucovorin | BRAF V600E-mutant Colorectal Cancer Study of Encorafenib Taken With Cetuximab Plus or Minus Chemotherapy (BREAKWATER) | Recruiting | USA | 17 |
| NCT04390243 | Phase II | Binimetinib + Encorafenib | Binimetinib and Encorafenib for the Treatment of Pancreatic Cancer in Patients With a Somatic BRAF V600E Mutation | Recruiting | USA | 0 |
| NCT04171622 | Phase II | Lenvatinib + Pembrolizumab | Lenvatinib and Pembrolizumab for the Treatment of Stage IVB Locally Advanced and Unresectable or Stage IVC Metastatic Anaplastic Thyroid Cancer | Not yet recruiting | USA | 0 |
| NCT03865082 | Phase II | IMO-2125 + Ipilimumab + Nivolumab | Study of Tilsotolimod in Combination With Nivolumab and Ipilimumab for the Treatment of Solid Tumors (ILLUMINATE-206) | Recruiting | USA | 0 |
| NCT02915666 | Phase I | Dabrafenib + Digoxin + Trametinib | A Clinical Trial of Patients With Melanoma | Withdrawn | USA | 0 |
| NCT03803553 | Phase III | Binimetinib + Cetuximab + Encorafenib Nivolumab Fluorouracil + Irinotecan + Leucovorin | Identification and Treatment Of Micrometastatic Disease in Stage III Colon Cancer | Recruiting | USA | 0 |
| NCT02178722 | Phase Ib/II | Epacadostat + Pembrolizumab | Study to Explore the Safety, Tolerability and Efficacy of MK-3475 in Combination With INCB024360 in Participants With Selected Cancers | Completed | USA | 0 |
| NCT03334617 | Phase II | AZD9150 + Durvalumab Durvalumab + Olaparib Cediranib + Durvalumab Durvalumab + Vistusertib Durvalumab + Trastuzumab deruxtecan Ceralasertib + Durvalumab | Phase II Umbrella Study of Novel Anti-cancer Agents in Patients With NSCLC Who Progressed on an Anti-PD-1/PD-L1 Containing Therapy (HUDSON) | Recruiting | USA | CAN | 6 |
| NCT03639714 | Phase Ib/II | GRT-C901 + GRT-R902 + Ipilimumab + Nivolumab | A Study of a Personalized Neoantigen Cancer Vaccine | Active, not recruiting | USA | 1 |
| NCT01943422 | Phase Ib/II | Interferon alpha-2b + Vemurafenib | Safety and Efficacy Study of Vemurafenib and High-dose Interferon Alfa-2b in Melanoma | Completed | USA | 0 |
| NCT05064280 | Phase II | Lenvatinib Pembrolizumab | Phase II Study of Pembrolizumab in Combination With Lenvatinib in Patients With TNBC, NSCLC, and Other Tumor Types and Brain Metastases | Not yet recruiting | USA | 0 |
| NCT02034110 | Phase II | Dabrafenib + Trametinib | Efficacy and Safety of the Combination Therapy of Dabrafenib and Trametinib in Subjects With BRAF V600E- Mutated Rare Cancers | Completed | USA | CAN | 12 |
| NCT05059470 | Phase II | Pembrolizumab | IMRT Followed by Pembrolizumab in the Adjuvant Setting in Anaplastic Cancer of the Thyroid (IMPAACT): Phase II Trial Adjuvant Pembrolizumab After IMRT in ATC | Not yet recruiting | USA | 0 |
| NCT04324112 | Phase II | Binimetinib + Encorafenib | Encorafenib Plus Binimetinib for People With BRAF V600E Mutated Relapsed/Refractory HCL | Recruiting | USA | 0 |
| NCT01876641 | Phase Ib/II | Decitabine + Vemurafenib | Treatment of a Resistant Disease Using Decitabine Combined With Vemurafenib | Terminated | USA | 0 |
| NCT04623775 | Phase II | Cisplatin + Nab-paclitaxel + Nivolumab + Pemetrexed Disodium Cisplatin + Nivolumab + Paclitaxel + Pemetrexed Disodium Carboplatin + Nab-paclitaxel + Nivolumab + Pemetrexed Disodium Carboplatin + Nivolumab + Paclitaxel + Pemetrexed Disodium Cisplatin + Nab-paclitaxel + Nivolumab + Pemetrexed Disodium + Relatlimab Cisplatin + Nivolumab + Paclitaxel + Pemetrexed Disodium + Relatlimab Carboplatin + Nab-paclitaxel + Nivolumab + Pemetrexed Disodium + Relatlimab Carboplatin + Nivolumab + Paclitaxel + Pemetrexed Disodium + Relatlimab | A Study of Relatlimab Plus Nivolumab in Combination With Chemotherapy vs. Nivolumab in Combination With Chemotherapy as First Line Treatment for Participants With Stage IV or Recurrent Non-small Cell Lung Cancer (NSCLC) | Recruiting | USA | 20 |
| NCT04083976 | Phase II | Erdafitinib | A Study of Erdafitinib in Participants With Advanced Solid Tumors and Fibroblast Growth Factor Receptor (FGFR) Gene Alterations | Recruiting | USA | 14 |
| NCT04166409 | Phase III | Selumetinib Carboplatin + Vincristine Sulfate | A Study of the Drugs Selumetinib vs. Carboplatin and Vincristine in Patients With Low-Grade Glioma | Recruiting | USA | CAN | 1 |
| NCT04151563 | Phase Ib/II | Lucitanib + Nivolumab Docetaxel Cabozantinib + Nivolumab Cabozantinib + Ipilimumab + Nivolumab Docetaxel + Nivolumab Docetaxel + Nivolumab + Ramucirumab | A Phase 1/2 Study Evaluating Multiple Nivolumab Combination Therapy in Participants With Stage IV Non-small Cell Lung Cancer That Has Spread or Has Reoccurred After Failure of Chemotherapy and Immunotherapy | Withdrawn | USA | 12 |