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| Profile Name | BRAF mutant |
| Gene Variant Detail | |
| Relevant Treatment Approaches |
| Molecular Profile | Indication/Tumor Type | Response Type | Relevant Treatment Approaches | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|---|
| BRAF mutant | Advanced Solid Tumor | sensitive | Dabrafenib | Phase I | Actionable | In a Phase I clinical trial, Tafinlar (dabrafenib) demonstrated safety and efficacy in patients with BRAF V600E positive solid tumors (PMID: 22608338). | 22608338 | |
| BRAF mutant | melanoma | sensitive | PLX8394 | Preclinical | Actionable | In a preclinical study, PLX8394 blocked survival and growth of vemurafenib/PLX4720-resistant melanoma cells harboring BRAF V600E splice variants in culture (PMID: 24422853). | 24422853 | |
| BRAF mutant | pancreatic adenocarcinoma | sensitive | Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of human pancreatic adenocarcinoma cells harboring mutant BRAF in culture (PMID: 26343583). | 26343583 | |
| BRAF mutant | melanoma | predicted - sensitive | 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 BRAF-mutant melanoma cell lines in culture, and inhibited tumor growth melanoma cell line xenograft models harboring BRAF mutations, including models with BRAF inhibitor resistance (PMID: 25873592). | 25873592 | |
| BRAF mutant | melanoma | sensitive | Palbociclib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring a BRAF mutation demonstrated greater sensitivity to the combination treatment of Mekinist (trametinib) and Ibrance (palbociclib) in culture when compared to either agent alone (PMID: 27488531). | 27488531 | |
| BRAF mutant | colorectal cancer | sensitive | MLN2480 | Preclinical | Actionable | In a preclinical study, MLN2480 demonstrated efficacy in BRAF mutant xenograft models of melanoma and colorectal cancer (J Clin Oncol 31, 2013 (suppl; abstr e13529)). | detail... | |
| BRAF mutant | melanoma | sensitive | Encorafenib | Phase I | Actionable | In a Phase I trial, Encorafenib (LGX818) treatment resulted in an overall response rate (ORR) of 60% (15/25) and a median progression-free survival (mPFS) of 12.4 months in BRAF inhibitor-naïve melanoma patients harboring BRAF mutations, and an ORR of 22% (6/29) and mPFS of 1.9 months in BRAF inhibitor-pretreated patients (PMID: 28611198; NCT01436656). | 28611198 | |
| BRAF mutant | colorectal cancer | decreased response | PLX4720 | Preclinical - Cell culture | Actionable | In a preclinical study, BRAF mutant colorectal cancer cell lines demonstrated reduced sensitivity to PLX4720 in culture (PMID: 26351322). | 26351322 | |
| BRAF mutant | colorectal cancer | no benefit | Regorafenib | Phase II | Actionable | In a Phase II clinical trial (PREVIUM), Stivarga (regorafenib) treatment resulted in 0% (0/15) 6-month progression free survival (PFS), a 2.2-month median PFS, and a median overall survival of 3.3 months in metastatic colorectal cancer patients with KRAS (n=9), NRAS (n=3) or BRAF (n=2) mutations who failed first line therapy; however, the trial was terminated early due to poor accrual (PMID: 30120161; NCT02175654). | 30120161 | |
| BRAF mutant | melanoma | predicted - sensitive | Belvarafenib | Phase I | Actionable | In Phase I trials, Belvarafenib (HM95573) treatment resulted in partial response in a patients with BRAF-mutant melanoma in a dose escalation study, and partial response in 33% (2/6) of BRAF-mutant melanoma patients in a dose expansion study (J Clin Oncol 37, 2019 (suppl; abstr 3000); NCT02405065, NCT03118817). | detail... | |
| BRAF mutant | melanoma | sensitive | MLN2480 | Phase I | Actionable | In a Phase I trial, MLN2480 resulted in a median progression free survival of 4.6 months and a partial response in 50% (8/16) of melanoma patients harboring a BRAF mutation (Ann Oncol 2017, Vol 28, Suppl 5, Abstract # 410P; NCT01425008). | detail... | |
| BRAF mutant | melanoma | sensitive | MLN2480 | Preclinical | Actionable | In a preclinical study, MLN2480 demonstrated efficacy in BRAF mutant xenograft models of melanoma and colorectal cancer (J Clin Oncol 31, 2013 (suppl; abstr e13529)). | detail... | |
| BRAF mutant | colorectal cancer | sensitive | AZ628 + Selumetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Koselugo (selumetinib) and AZ628 synergistically inhibited Mapk signaling and cell proliferation in BRAF mutant colorectal cancer cell lines in culture (PMID: 26351322). | 26351322 | |
| BRAF mutant | Advanced Solid Tumor | no benefit | Trametinib | Phase II | Actionable | In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion (n=1) or non-V600 mutations (n=31), resulted in a partial response in 3% (1/32) and stable disease in 31% (10/32) of the patients, with a median progression-free survival of 1.8 months, and a median overall survival of 5.7 months (PMID: 31924734; NCT02465060). | 31924734 | |
| BRAF mutant | melanoma | sensitive | PET-16 + Vemurafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, PET-16 and Zelboraf (vemurafenib) synergistically inhibited growth of melanoma cell lines in culture, resulted in enhanced tumor growth inhibition in cell ine xenograft models (PMID: 26984758). | 26984758 | |
| BRAF mutant | lung non-small cell carcinoma | predicted - sensitive | unspecified PD-1 antibody | Clinical Study - Cohort | Actionable | In a clinical study, mutant BRAF correlated with prolonged duration on immune checkpoint inhibitor therapy compared to wild-type BRAF in non-small cell lung cancer patients (Ann Oncol 2017, Vol 28, Suppl 5, Abstract #1138PD). | detail... | |
| BRAF mutant | Advanced Solid Tumor | sensitive | Obatoclax | Preclinical | Actionable | In a preclinical study, obatoclax decreased proliferation in human tumor cell lines with BRAF mutation in culture (PMID: 22460902). | 22460902 | |
| BRAF mutant | melanoma | predicted - sensitive | ST-162 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, ST-162 treatment resulted in tumor regression in BRAF mutant-melanoma cell line xenograft models (PMID: 28775144). | 28775144 | |
| BRAF mutant | Advanced Solid Tumor | predicted - sensitive | Binimetinib + Encorafenib | Phase II | Actionable | In a Phase II trial (BEAVER), Mektovi (binimetinib) and Braftovi (encorafenib) combination therapy demonstrated safety and preliminary efficacy in patients with advanced solid tumors harboring BRAF non-V600E mutations, resulting in an objective response rate of 12.5% (1/8), BRAF mutations including class 1 (n=1), class 2 (n=3), and class 3 (n=5) (J Clin Oncol 39, no. 15_suppl, abstr e15038; NCT03839342). | detail... | |
| BRAF mutant | melanoma | sensitive | S63845 + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, combination of S63845 and Mekinist (trametinib) resulted in potent cytotoxic effects in BRAF-mutated melanoma cells in culture compared to the cytostatic effect of Mekinist (trametinib) alone (PMID: 27760111). | 27760111 | |
| BRAF mutant | melanoma | sensitive | Tubastatin A | Preclinical | Actionable | In a preclinical study, Tubastatin A inhibited proliferation of BRAF mutant melanoma cell lines in culture (PMID: 25957812). | 25957812 | |
| BRAF mutant | colon cancer | predicted - sensitive | Selumetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Selumetinib (AZD6244) resulted in some reduced cell growth in colon cancer cells harboring a BRAF mutation in culture (PMID: 27655129). | 27655129 | |
| BRAF mutant | colorectal cancer | predicted - resistant | SYM004 | Preclinical - Pdx | Actionable | In a preclinical study, patient-derived xenograft (PDX) models of colorectal cancer harboring KRAS, NRAS or BRAF mutations demonstrated poor response to SYM004 treatment compared to wild-type models (PMID: 29423521). | 29423521 | |
| BRAF mutant | Advanced Solid Tumor | predicted - sensitive | KO-947 | Preclinical - Pdx | Actionable | In a preclinical study, KO-947 resulted in tumor regression in patient derived xenograft (PDX) models harboring either a BRAF mutation, NRAS mutation, or KRAS mutation (EJC Dec 2016, 69:1; S126). | detail... | |
| BRAF mutant | colon cancer | predicted - sensitive | PF-00477736 + PF3644022 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Chk1 inhibitor PF-477736 and MK2 inhibitor PF3644022 synergistically inhibited tumor growth in cell line xenograft models of BRAF mutant colon cancer (PMID: 26140595). | 26140595 | |
| BRAF mutant | lung non-small cell carcinoma | predicted - sensitive | KO-947 | Preclinical - Pdx | Actionable | In a preclinical study, KO-947 inhibited Erk signaling and induced tumor regression in patient-derived xenograft models of BRAF-mutant non-small cell lung cancer harboring (Cancer Res 2017;77(13 Suppl):Abstract nr 5168). | detail... | |
| BRAF mutant | splenic marginal zone lymphoma | not applicable | N/A | Guideline | Diagnostic | BRAF mutations aid in the diagnosis of splenic marginal zone lymphoma (NCCN.org). | detail... | |
| BRAF mutant | melanoma | predicted - sensitive | KO-947 | Preclinical - Pdx | Actionable | In a preclinical study, KO-947 inhibited Erk signaling and induced tumor regression in patient-derived xenograft models of BRAF-mutant melanoma (Cancer Res 2017;77(13 Suppl):Abstract nr 5168). | detail... | |
| BRAF mutant | thyroid gland cancer | sensitive | Belvarafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Belvarafenib (HM95573) inhibited growth of BRAF mutant thyroid cancer cells in culture (Cancer Res 2015;75(15 Suppl):Abstract nr 2607). | detail... | |
| BRAF mutant | colorectal cancer | sensitive | Cetuximab + LSN3074753 | Preclinical - Pdx | Actionable | In a preclinical study, LSN3074753 and Erbitux (cetuximab) synergistically inhibited tumor growth in patient-derived xenograft models of colorectal cancer harboring BRAF mutations, resulted in a disease control rate of 41.7% (5/12) (PMID: 28611205). | 28611205 | |
| BRAF mutant | multiple myeloma | sensitive | Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of human multiple myeloma cells harboring mutant BRAF in culture (PMID: 26343583). | 26343583 | |
| BRAF mutant | melanoma | sensitive | S63845 + Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, combination of S63845 and Zelboraf (vemurafenib) resulted in potent cytotoxic effects in BRAF-mutated melanoma cells in culture compared to the cytostatic effect of Zelboraf (vemurafenib) alone (PMID: 27760111). | 27760111 | |
| BRAF mutant | Advanced Solid Tumor | sensitive | RAF709 | Preclinical - Cell culture | Actionable | In a preclinical study, cancer cell lines harboring BRAF mutations demonstrated increased sensitivity to RAF709 compared to BRAF wild-type cells in culture (PMID: 29343524). | 29343524 | |
| BRAF mutant | colorectal cancer | sensitive | Alpelisib + Cetuximab + Encorafenib | Phase Ib/II | Actionable | In a Phase Ib/II trial, the triple combination therapy of Encorafenib (LGX818), Erbitux (cetuximab), and Alpelisib (BYL719) resulted in an overall response rate of 18% (5/28), including 5 patients with a partial response, and led to a median progression free survival of 4.2 months and response duration of 12 weeks (PMID: 28363909). | detail... 28363909 | |
| BRAF mutant | lymphoma | no benefit | Trametinib | Phase II | Actionable | In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion (n=1) or non-V600 mutations (n=31), resulted in a partial response in 3% (1/32) and stable disease in 31% (10/32) of the patients, with a median progression-free survival of 1.8 months, and a median overall survival of 5.7 months (PMID: 31924734; NCT02465060). | 31924734 | |
| BRAF mutant | thyroid gland cancer | predicted - sensitive | Selumetinib | Phase I | Actionable | In a Phase I study, Koselugo (selumetinib) demonstrated an increase in iodine uptake and retention in a subgroup of patients with thyroid cancer that was refractory to radioiodine, including patients with BRAF and NRAS mutations (PMID: 23406027). | 23406027 | |
| BRAF mutant | lung adenocarcinoma | sensitive | Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of lung adenocarcinoma cells harboring mutant BRAF in culture (PMID: 26343583). | 26343583 | |
| BRAF mutant | Advanced Solid Tumor | no benefit | LY3009120 | Case Reports/Case Series | Actionable | In a Phase I trial, LY3009120 did not achieve expected pharmacodynamic effects, resulted in stable disease as best overall response in 5 of 12 patients with advanced or metastatic cancer harboring BRAF mutations (PMID: 31645440; NCT02014116). | 31645440 | |
| BRAF mutant | melanoma | sensitive | E6201 | Preclinical | Actionable | In a preclinical study, E6201 inhibited proliferation of several melanoma cell lines in culture and hypersensitivity was associated with BRAF mutations (PMID: 23039341). | 23039341 | |
| BRAF mutant | colorectal cancer | predicted - sensitive | SY-5609 | Preclinical - Pdx | Actionable | In a preclinical study, SY-5609 treatment resulted in 90% or more tumor growth inhibition or tumor regression in 50% (5/10) of patient-derived xenograft (PDX) models of colorectal cancer harboring BRAF mutations (J Clin Oncol 38: 2020 (suppl; abstr 3585)). | detail... | |
| BRAF mutant | melanoma | sensitive | Binimetinib + Buparlisib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Binimetinib (MEK162) and Buparlisib (BKM120) resulted in improved cell growth inhibition compared to either agent alone in a metastatic melanoma cell line harboring a BRAF mutation in culture (PMID: 27307593). | 27307593 | |
| BRAF mutant | Advanced Solid Tumor | predicted - sensitive | PF-00477736 + PF3644022 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Chk1 inhibitor PF-477736 and MK2 inhibitor PF3644022 synergistically inhibited growth of various cancer cell lines harboring BRAF mutations in culture and in cell line xenograft models (PMID: 26140595). | 26140595 | |
| BRAF mutant | colorectal cancer | predicted - sensitive | KO-947 | Preclinical - Pdx | Actionable | In a preclinical study, KO-947 inhibited Erk signaling and induced tumor regression in patient-derived xenograft models of BRAF-mutant colorectal cancer (Cancer Res 2017;77(13 Suppl):Abstract nr 5168). | detail... | |
| BRAF mutant | cervix carcinoma | predicted - sensitive | KO-947 | Preclinical - Pdx | Actionable | In a preclinical study, KO-947 inhibited Erk signaling and induced tumor regression in patient-derived xenograft models of BRAF-mutant cervical carcinoma (Cancer Res 2017;77(13 Suppl):Abstract nr 5168). | detail... | |
| BRAF mutant | colorectal cancer | sensitive | Belvarafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Belvarafenib (HM95573) inhibited growth of BRAF mutant colorectal cancer cell lines in culture and in cell line xenograft models (Cancer Res 2015;75(15 Suppl):Abstract nr 2607). | detail... | |
| BRAF mutant | Advanced Solid Tumor | predicted - sensitive | LXH 254 | Case Reports/Case Series | Actionable | In a Phase I trial, LXH 254 treatment resulted in partial response in 2.6% (2/75) and stable disease in 33% (25/75) of patients with advanced solid tumors harboring MAPK pathway alterations, one of the patient achieved partial response harbored a BRAF mutation (J Clin Oncol 36, no. 15_suppl (May 20 2018) 2586-2586; NCT02607813). | detail... | |
| BRAF mutant | lung non-small cell carcinoma | predicted - sensitive | unspecified PD-L1 antibody | Clinical Study - Cohort | Actionable | In a clinical study, mutant BRAF correlated with prolonged duration on immune checkpoint inhibitor therapy compared to wild-type BRAF in non-small cell lung cancer patients (Ann Oncol 2017, Vol 28, Suppl 5, Abstract #1138PD). | detail... | |
| BRAF mutant | Advanced Solid Tumor | decreased response | XL147 | Preclinical | Actionable | In a preclinical study, tumor cell lines harboring BRAF mutations demonstrated limited sensitivity to XL147 treatment in culture (PMID: 25637314). | 25637314 | |
| BRAF mutant | colorectal cancer | sensitive | Cetuximab + Encorafenib | Phase Ib/II | Actionable | In a Phase Ib/II trial, the combination therapy of Erbitux (cetuximab) and Encorafenib (LGX818) in colorectal cancer patients harboring a BRAF mutation resulted in an overall response rate of 19% (5/26), including 1 patient with a complete response and 4 patients with a partial response, and led to a median progression free survival of 3.7 months and response duration of 46 weeks (PMID: 28363909). | 28363909 | |
| BRAF mutant | Advanced Solid Tumor | no benefit | CC-90003 | Phase I | Actionable | In a Phase Ia trial, CC-90003 treatment did not result in any objective responses and demonstrated toxicity in advanced solid tumor patients harboring KRAS, NRAS, or BRAF mutations (AJ Clin Oncol 35, 2017 (suppl; abstr 2577)). | detail... | |
| BRAF mutant | lung non-small cell carcinoma | unknown | unspecified immune checkpoint inhibitor | Clinical Study | Actionable | In a retrospective clinical study, no significant difference in overall survival (19.0 vs 18.4 months) was found in patients with non-small cell lung cancer harboring BRAF V600E (n=14), amplification (n=5), or non-V600E mutations (n=12) who received immunotherapy compared to those who never received immunotherapy (PMID: 31367539). | 31367539 | |
| BRAF mutant | 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 non-V600E (n=5) mutations, although RTD type was not associated with OS in a univariate analysis (PMID: 30268448). | 30268448 | |
| BRAF mutant | melanoma | predicted - sensitive | UNC2025 + Vemurafenib | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, the combination therapy of UNC2025 and Zelboraf (vemurafenib) resulted in greater inhibition of colony formation and apoptotic induction in melanoma cells harboring a BRAF mutation in culture and led to a higher degree of tumor growth inhibition in a patient derived xenograft (PDX) model of melanoma with a BRAF mutation when compared to either therapy alone (PMID: 30482852). | 30482852 | |
| BRAF mutant | colorectal cancer | predicted - sensitive | Binimetinib | Phase I | Actionable | In a Phase I trial, Binimetinib (MEK162) treatment resulted in an estimated progression free survival of 1.4 months and overall survival of 7.1 months in colorectal cancer patients harboring BRAF mutations (PMID: 28152546). | 28152546 | |
| BRAF mutant | lung non-small cell carcinoma | predicted - sensitive | Dabrafenib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, treatment with the combination of Mekinist (trametinib) and Tafinlar (dabrafenib) resulted in decreased proliferation and increased apoptosis and enhanced ERK inhibition compared to either agent alone in non-small cell lung cancer cell lines harboring non-BRAF V600 mutations in culture (PMID: 28947956). | 28947956 | |
| BRAF mutant | colorectal cancer | resistant | Trametinib | Preclinical | Actionable | In a preclinical study, a majority of human colorectal cancer cell lines (4/7) harboring mutant BRAF were insensitive to Mekinist (trametinib) in culture (PMID: 26343583). | 26343583 | |
| BRAF mutant | stomach carcinoma | predicted - sensitive | KO-947 | Preclinical - Pdx | Actionable | In a preclinical study, KO-947 inhibited Erk signaling and induced tumor regression in patient-derived xenograft models of BRAF-mutant gastric carcinoma (Cancer Res 2017;77(13 Suppl):Abstract nr 5168). | detail... | |
| BRAF mutant | melanoma | sensitive | Vemurafenib + Voruciclib | Phase I | Actionable | In a Phase I trial, Voruciclib (P1446A-05) and Zelboraf (vemurafenib) combination therapy demonstrated safety and preliminary efficacy, resulted in complete response in 33% (1/3) and partial response in 67% (2/3) of BRAFi-naïve melanoma patients harboring BRAF mutations (J Clin Oncol 33, 2015 (suppl; abstr 9076)). | detail... | |
| BRAF mutant | Advanced Solid Tumor | predicted - sensitive | MLN2480 | Preclinical - Cell culture | Actionable | In a preclinical study, MLN2480 inhibited downstream signaling and proliferation of several BRAF mutant solid tumor cell lines in culture (EJC Supp, Nov 2010, Vol 8(7), p40-41). | detail... | |
| BRAF mutant | melanoma | sensitive | E6201 + LY294002 | Preclinical | Actionable | In a preclinical study, E6201 and LY294002 synergistically inhibited proliferation of melanoma cell lines harboring BRAF mutations in culture, regardless of PTEN mutation status (PMID: 23039341). | 23039341 | |
| BRAF mutant | melanoma | sensitive | Buparlisib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Buparlisib (BKM120) treatment in human melanoma cell line xenograft models with brain metastases and harboring a BRAF mutation resulted in inhibition of brain tumor growth (PMID: 27307593). | 27307593 | |
| BRAF mutant | colorectal cancer | predicted - sensitive | LSN3074753 | Preclinical - Pdx | Actionable | In a preclinical study, LSN3074753 resulted in a disease control rate of 8.3% (1/12) in BRAF mutant patient-derived xenograft models of colorectal cancer (PMID: 28611205). | 28611205 | |
| BRAF mutant | melanoma | predicted - sensitive | Ulixertinib | Phase I | Actionable | In a Phase I trial, treatment with BVD-523 (ulixertinib) resulted in a best response of stable disease in six melanoma patients and a partial response in three melanoma patients all harboring a BRAF mutation (PMID: 29247021). | 29247021 | |
| BRAF mutant | melanoma | sensitive | Buparlisib + Encorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Buparlisib (BKM120) and Encorafenib (LGX818) resulted in improved cell growth inhibition compared to either agent alone in a metastatic melanoma cell line harboring a BRAF mutation in culture (PMID: 27307593). | 27307593 | |
| BRAF mutant | pancreatic cancer | predicted - sensitive | KO-947 | Preclinical - Pdx | Actionable | In a preclinical study, KO-947 inhibited Erk signaling and induced tumor regression in patient-derived xenograft models of BRAF-mutant pancreatic cancer (Cancer Res 2017;77(13 Suppl):Abstract nr 5168). | detail... | |
| BRAF mutant | colorectal cancer | predicted - sensitive | Dabrafenib + Panitumumab + Trametinib | Phase Ib/II | Actionable | In a Phase I/II trial, treatment with the triple combination of Tafinlar (dabrafenib), Mekinist (trametinib), and Vectibix (panitumumab) resulted in an objective response rate (ORR) of 21% and median progression-free survival (mPFS) of 4.2 mo, compared with 0% ORR and mPFS of 2.6 mo with Mekinist (trametinib) plus Vectibix (panitumumab), and 10% ORR and mPFS of 3.5 mo with Tafinlar (dabrafenib) plus Vectibix (panitumumab) in patients with BRAF-mutant colorectal cancer (PMID: 27770002; NCT01750918). | 27770002 | |
| BRAF mutant | melanoma | sensitive | Selumetinib | Case Reports/Case Series | Actionable | In a Phase II trial, 5 out of 6 patients with advanced melanoma exhibiting a response to Koselugo (selumetinib) had BRAF-mutant tumors (PMID: 22048237). | 22048237 |
| Clinical Trial | Phase | Therapies | Title | Recruitment Status | Covered Countries | Other Countries |
|---|---|---|---|---|---|---|
| NCT01351103 | Phase I | LGK974 LGK974 + Spartalizumab | A Study of LGK974 in Patients With Malignancies Dependent on Wnt Ligands | Recruiting | USA | 2 |
| NCT03839342 | Phase II | Binimetinib + Encorafenib | Binimetinib and Encorafenib for the Treatment of Advanced Solid Tumors With Non-V600E BRAF Mutations (BEAVER) | Recruiting | CAN | 0 |
| NCT03415126 | Phase I | ASN007 | A Study of ASN007 in Patients With Advanced Solid Tumors | Completed | 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 | |
| NCT01877811 | Phase Ib/II | RXDX-105 | CEP-32496 in Patients With Advanced Solid Tumors in Phase 1 and Advanced Melanoma and Metastatic Colorectal Cancer in Phase 2 | Completed | USA | 0 |
| NCT03396497 | Phase I | LYC-55716 + Pembrolizumab | Study of LYC-55716 With Pembrolizumab in Adult Subjects With Non-Small Cell Lung Cancer | Unknown status | USA | 0 |
| NCT04072198 | Phase II | Bevacizumab + Fluorouracil + Irinotecan + Leucovorin + Nivolumab + Oxaliplatin | Nivolumab Plus FOLFOXIRI/Bevacizumab in First Line Chemotherapy of Advanced Colorectal Cancer RASm/BRAFm Patients (NIVACOR) | Recruiting | 1 | |
| NCT01037790 | Phase II | Palbociclib | PHASE II TRIAL OF THE CYCLIN-DEPEDENT KINASE INHIBITOR PD 0332991 IN PATIENTS WITH CANCER | Completed | USA | 0 |
| NCT03175224 | Phase Ib/II | Bozitinib | APL-101 Study of Subjects With NSCLC With c-Met EXON 14 Skip Mutations and c-Met Dysregulation Advanced Solid Tumors (SPARTA) | Recruiting | USA | CAN | 12 |
| NCT03037385 | Phase Ib/II | Pralsetinib | Phase 1/2 Study of the Highly-selective RET Inhibitor, Pralsetinib (BLU-667), in Patients With Thyroid Cancer, Non-Small Cell Lung Cancer, and Other Advanced Solid Tumors (ARROW) | Recruiting | USA | 12 |
| NCT02974725 | Phase I | LXH 254 + Ribociclib LXH 254 + Trametinib LTT462 + LXH 254 | A Phase Ib Study of LXH254-centric Combinations in NSCLC or Melanoma | Recruiting | USA | 10 |
| NCT03784378 | Phase I | RXDX-105 | Continued Access to RXDX-105 | Completed | USA | 0 |
| NCT03555149 | Phase Ib/II | Atezolizumab Atezolizumab + Isatuximab Atezolizumab + Bevacizumab + PGG beta-glucan | A Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Patients With Metastatic Colorectal Cancer (Morpheus-CRC) | Recruiting | USA | 6 |
| NCT01531361 | Phase I | Sorafenib + Vemurafenib Crizotinib + Vemurafenib | Vemurafenib With Sorafenib Tosylate or Crizotinib in Treating Patients With Advanced Malignancies With BRAF Mutations | Completed | USA | 0 |
| NCT02747537 | Phase II | Irinotecan + Sorafenib | Treating Relapsed/Recurrent/Refractory Pediatric Solid Tumors With Sorafenib in Combination With Irinotecan | Withdrawn | 0 | |
| NCT03978611 | Phase I | Ipilimumab + Relatlimab | A Study to Assess Safety and Efficacy of Relatlimab With Ipilimumab in Participants With Advanced Melanoma Who Progressed on Anti-PD-1 Treatment | Recruiting | USA | CAN | 4 |
| NCT02428712 | Phase Ib/II | PLX8394 | A Study of PLX8394 as a Single Agent in Patients With Advanced Unresectable Solid Tumors | Recruiting | USA | 0 |
| NCT01723202 | Phase II | Dabrafenib + Trametinib Dabrafenib | Dabrafenib With or Without Trametinib in Treating Patients With Recurrent Thyroid Cancer | Active, not recruiting | USA | 0 |
| NCT03559049 | Phase Ib/II | Carboplatin + Pembrolizumab + Pemetrexed Disodium + Rucaparib | Rucaparib and Pembrolizumab for Maintenance Therapy in Stage IV Non-Squamous Non-Small Cell Lung Cancer | Recruiting | USA | 0 |
| NCT04524689 | Phase II | Carboplatin + Pembrolizumab + SAR408701 Pembrolizumab + SAR408701 Cisplatin + Pembrolizumab + SAR408701 Pembrolizumab | SAR408701 in Combination With Pembrolizumab and Pembrolizumab Alone in Patients With Non-squamous Non-small Cell Lung Cancer (NSQ NSCLC) (CARMEN-LC05) | Recruiting | USA | 6 |
| NCT04425239 | Phase II | Fluorouracil + Irinotecan + Leucovorin + Panitumumab | Intermittent or Continuous Panitumumab Plus FOLFIRI for RAS/B-RAF Wild-type Metastatic Colorectal Cancer (IMPROVE) | Active, not recruiting | 1 | |
| NCT04566393 | Expanded access | Ulixertinib | Expanded Access to Ulixertinib (BVD-523) in Patients With Advanced MAPK Pathway-Altered Malignancies | Available | USA | 0 |
| 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 |
| NCT02857270 | Phase I | LY3214996 Gemcitabine + LY3214996 + Nab-paclitaxel LY3214996 + Midazolam Abemaciclib + LY3214996 | A Study of LY3214996 Administered Alone or in Combination With Other Agents in Participants With Advanced/Metastatic Cancer | Active, not recruiting | USA | 3 |
| NCT04129515 | Phase Ib/II | Pembrolizumab | NovoTTF-200A + Pembrolizumab In Melanoma Brain Metastasis | Recruiting | USA | 0 |
| NCT03698994 | Phase II | Ulixertinib | Ulixertinib in Treating Patients With Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With MAPK Pathway Mutations (A Pediatric MATCH Treatment Trial) | Active, not recruiting | USA | 1 |
| NCT04776655 | Phase III | Bevacizumab + Fluorouracil + Irinotecan + Leucovorin Cetuximab + Fluorouracil + Irinotecan + Leucovorin | Study in mCRC Patients RAS/BRAF wt Tissue and RAS Mutated LIquid BIopsy to Compare FOLFIRI Plus CetuxiMAb or BevacizumaB (LIBImAb) | Recruiting | 1 | |
| NCT03992456 | Phase II | Panitumumab Regorafenib Trifluridine-tipiracil hydrochloride | Panitumumab, Regorafenib, or TAS-102, in Treating Patients With Metastatic and/or Unresectable RAS Wild-Type Colorectal Cancer | Recruiting | USA | 0 |
| NCT02610361 | Phase I | BGB-283 | Study of the Safety and Pharmacokinetics of BGB-283 in Patients With Solid Tumors | Completed | 2 | |
| NCT00770263 | Phase I | Erlotinib + Temsirolimus | Erlotinib and Temsirolimus for Solid Tumors | Completed | USA | 0 |
| NCT01449058 | Phase Ib/II | Alpelisib + Binimetinib | A Phase Ib Study of MEK162 Plus BYL719 in Adult Patients With Selected Advanced Solid Tumors | Completed | USA | 6 |
| NCT04457284 | Phase II | Cisplatin + Nivolumab + Temozolomide | Temozolomide, Cisplatin, and Nivolumab in People With Colorectal Cancer | Recruiting | USA | 0 |
| NCT03218826 | Phase I | AZD8186 + Docetaxel | PI3Kbeta Inhibitor AZD8186 and Docetaxel in Treating Patients Advanced Solid Tumors With PTEN or PIK3CB Mutations That Are Metastatic or Cannot Be Removed by Surgery | Active, not recruiting | USA | 0 |
| NCT01841463 | Phase Ib/II | Vemurafenib + Voruciclib | Study of an Oral Cdk Inhibitor Administered With an Oral BRAF Inhibitor in Patients With Advanced or Inoperable Malignant Melanoma With BRAF Mutation | Suspended | USA | 0 |
| NCT04488003 | Phase II | Ulixertinib | Study of Ulixertinib for Patients With Advanced Malignancies Harboring MEK or Atypical BRAF Alterations | Recruiting | USA | 0 |
| NCT01781429 | Phase Ib/II | Ulixertinib | Phase I Dose-Escalation, Safety, Pharmacokinetic and Pharmacodynamic Study of BVD-523 in Patients With Advanced Malignancies | Completed | USA | 0 |
| NCT02050321 | Phase II | Acitretin + Vemurafenib | A Phase II Study of Vemurafenib Combined With Acitretin in Patients With Advanced Melanoma | Terminated | USA | 0 |
| NCT04409639 | Phase II | Cobimetinib | Cobimetinib in Newly Diagnosed or HMA-treated CMML Patients With RAS Pathway Mutations (CONCERTO) | Recruiting | USA | 0 |
| NCT03696212 | Phase Ib/II | Grapiprant + Pembrolizumab | Grapiprant (ARY-007) and Pembrolizumab in Patients With Advanced or Metastatic Post-PD-1/L1 NSCLC Adenocarcinoma | Terminated | USA | 0 |
| NCT03091257 | Phase I | Dabrafenib + Trametinib Dabrafenib Trametinib | A Study of Dabrafenib and/or Trametinib in Patients With Relapsed and/or Refractory Multiple Myeloma | Recruiting | USA | 0 |
| NCT04515394 | Phase II | Cetuximab + Tepotinib | Study of Tepotinib Combined With Cetuximab in Participants Left-Sided Metastatic Colorectal Cancer (mCRC) Acquired Resistance Due to Mesenchymal Epithelial Transition (MET) Amplification | Active, not recruiting | USA | 7 |
| NCT02648490 | Phase I | Acetaminophen + Dexamethasone + Diphenhydramine + Ondansetron HLX07 | An Open-label, Phase 1 Study to Determine the Maximum Tolerated Dose of HLX07,in Patients With Advanced Solid Cancers | Completed | USA | 1 |
| NCT04370704 | Phase Ib/II | INCAGN02385 + INCAGN02390 + Retifanlimab INCAGN02385 + INCAGN02390 | Study of Combination Therapy With INCMGA00012 (Anti-PD-1), INCAGN02385 (Anti-LAG-3), and INCAGN02390 (Anti-TIM-3) in Participants With Select Advanced Malignancies | Recruiting | USA | 0 |
| NCT04495621 | Phase Ib/II | Cetuximab + CH5132799 | MEN1611 With Cetuximab in Metastatic Colorectal Cancer (C-PRECISE-01) (C-PRECISE-01) | Recruiting | USA | 6 |
| 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 |
| NCT03391232 | Phase I | PolyPEPI1018 | Safety and Immunogenicity of PolyPEPI1018 Vaccine in the Treatment of Metastatic Colorectal Cancer (OBERTO) | Completed | USA | 1 |
| NCT01306045 | Phase II | Erlotinib Lapatinib MK2206 Sunitinib Selumetinib | Molecular Profiling and Targeted Therapy for Advanced Non-Small Cell Lung Cancer, Small Cell Lung Cancer, and Thymic Malignancies | Active, not recruiting | USA | 0 |
| NCT03272464 | Phase I | Dabrafenib + Itacitinib + Trametinib | INCB039110 in Combination With Dabrafenib and Trametinib in Patients With BRAF-mutant Melanoma and Other Solid Tumors. | Active, not recruiting | USA | 0 |
| NCT04145297 | Phase I | Hydroxychloroquine + Ulixertinib | Ulixertinib (BVD-523) and Hydroxychloroquine in Patients w Advanced MAPK-Mutated Gastrointestinal Adenocarcinomas (UTAH) | Recruiting | USA | 0 |
| NCT01744652 | Phase I | Crizotinib + Dasatinib | Dasatinib and Crizotinib in Advanced Cancer | Completed | USA | 0 |
| NCT01138085 | Phase I | Trametinib + Uprosertib | Safety, Pharmacokinetics (PK) of AKT and MEK Combination | Completed | USA | 0 |
| NCT02860780 | Phase I | Prexasertib + Ralimetinib | A Study of Prexasertib (LY2606368) in Combination With Ralimetinib in Participants With Advanced or Metastatic Cancer | Completed | USA | 1 |
| NCT03874026 | Phase II | Cetuximab + Fluorouracil + Irinotecan + Leucovorin | Study of Folfiri/Cetuximab in FcGammaRIIIa V/V Stage IV Colorectal Cancer Patients (CIFRA) | Recruiting | 1 | |
| NCT03162627 | Phase I | Olaparib + Selumetinib | Selumetinib and Olaparib in Solid Tumors | Recruiting | USA | 0 |
| NCT01885195 | Phase II | Binimetinib | MEK162 for Patients With RAS/RAF/MEK Activated Tumors | Completed | 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 |
| NCT04591431 | Phase II | Everolimus Nivolumab Itacitinib Erlotinib Ponatinib Pemigatinib Ipatasertib Ipilimumab Cobimetinib Atezolizumab Palbociclib Entrectinib Vemurafenib Lapatinib Trastuzumab Brigatinib Alectinib Ado-trastuzumab emtansine Pertuzumab Vismodegib | The Rome Trial From Histology to Target: the Road to Personalize Target Therapy and Immunotherapy (ROME) | Recruiting | 1 | |
| NCT04189055 | Phase II | Cetuximab + Irinotecan Cetuximab | Cetuximab as Salvage Therapy in Patients With Neo Wild-type RAS/RAF Metastatic Colorectal Cancer With Liver Metastases. (CETIDYL) | Recruiting | 1 | |
| NCT03714958 | Phase I | HDM201 + Trametinib | Trametinib + HDM201 in CRC Patients With RAS/RAF Mutant and TP53 Wild-type Advanced/Metastatic Colorectal Cancer Mutant and TP53 Wild-type (TRAHD) | Recruiting | 1 | |
| NCT04609566 | Phase II | Brentuximab vedotin + Pembrolizumab | Brentuximab Vedotin With Pembrolizumab in Metastatic Solid Tumors | Recruiting | USA | 0 |
| NCT01719380 | Phase Ib/II | Cetuximab + Encorafenib Alpelisib + Cetuximab + Encorafenib | Study of LGX818 and Cetuximab or LGX818, BYL719, and Cetuximab in BRAF Mutant Metastatic Colorectal Cancer | Completed | USA | CAN | 10 |
| NCT02296112 | Phase II | Trametinib | Trametinib in Treating Patients With Advanced Melanoma With BRAF Non-V600 Mutations | Completed | 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 |
| NCT03664024 | Phase II | Pembrolizumab + Pemetrexed Disodium Carboplatin + Pembrolizumab + Pemetrexed Disodium Cisplatin + Pembrolizumab + Pemetrexed Disodium | Biomarkers of Response to Pembrolizumab Combined With Chemotherapy in Non-Small Cell Lung Cancer (KEYNOTE-782, MK-3475-782) (KEYNOTE-782) | Completed | USA | CAN | 3 |
| NCT04511845 | Phase I | SPYK04 | A Dose-Escalation Study of SPYK04 in Patients With Locally Advanced or Metastatic Solid Tumors (With Expansion). | Recruiting | USA | 1 |
| NCT01231594 | Phase I | Dabrafenib Trametinib | A Rollover Study to Provide Continued Treatment With GSK2118436 to Subjects With BRAF Mutation-Positive Tumors | Completed | USA | CAN | 7 |
| NCT04105270 | Phase II | Carboplatin + Durvalumab + Pemetrexed Disodium Cisplatin + Durvalumab + Pemetrexed Disodium Durvalumab | P2 of RMT in Combo w Durvalumab or Durva + Chemo in Untreated Adenocarcinoma NSCLC | Not yet recruiting | USA | 0 |
| NCT04892017 | Phase I | DCC-3116 DCC-3116 + Trametinib | A Safety, Tolerability and PK Study of DCC-3116 in Patients With RAS or RAF Mutant Advanced or Metastatic Solid Tumors. | Recruiting | USA | 0 |
| NCT03972046 | Phase II | Dabrafenib + Talimogene laherparepvec + Trametinib | Neoadjuvant Use of Talimogene Laherparepvec and BRAF/MEK Inhibitor for Advanced Nodal BRAF Mutant Melanoma | Withdrawn | USA | 0 |
| NCT03051035 | Phase I | KO-947 | First-in-Human Study of KO-947 in Non-Hematological Malignancies | Terminated | USA | 1 |
| NCT04925986 | Phase II | MGCD516 + Pembrolizumab | Sitravatinib Plus Pembrolizumab in Patients With Advanced Treatment-Naïve PD-L1+ Non-Squamous NSCLC | Not yet recruiting | USA | 0 |
| NCT04270591 | Phase Ib/II | SCC244 | Assessment of Anti-tumor and Safety in Glumetinib in Patients With c-MET-positive Non-Small Cell Lung Cancer | Recruiting | USA | 2 |
| NCT04656652 | Phase III | Docetaxel DS-1062a | Study of DS-1062A Versus Docetaxel in Previously Treated Advanced or Metastatic Non-small Cell Lung Cancer Without Actionable Genomic Alterations (TROPION-LUNG01) | Recruiting | USA | CAN | 23 |
| NCT03475953 | Phase Ib/II | Avelumab + Regorafenib | A Phase I/II Study of Regorafenib Plus Avelumab in Solid Tumors (REGOMUNE) | Recruiting | 1 | |
| NCT03213691 | Phase II | Selumetinib | Selumetinib Sulfate in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Activating MAPK Pathway Mutations (A Pediatric MATCH Treatment Trial) | Active, not recruiting | USA | 1 |