Therapy Detail
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| Therapy Name | Vemurafenib |
| Synonyms | |
| Therapy Description |
Zelboraf (vemurafenib) inhibits BRAF V600E, wild-type BRAF, ARAF, and CRAF (PMID: 20179705), which may result in an inhibition of the MAPK signaling pathway resulting in a reduction of tumor cell proliferation (PMID: 20823850). Zelboraf (vemurafenib) is FDA approved for BRAF V600E-mutant melanoma and for BRAF V600-positive Erdheim-Chester disease (FDA.gov). |
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| Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
|---|---|---|---|---|
| Vemurafenib | Zelboraf | RO5185426|PLX4032 | RAF Inhibitor (Pan) 22 | Zelboraf (vemurafenib) inhibits BRAF V600E, wild-type BRAF, ARAF, and CRAF (PMID: 20179705), which may result in an inhibition of the MAPK signaling pathway resulting in a reduction of tumor cell proliferation (PMID: 20823850). Zelboraf (vemurafenib) is FDA approved for BRAF V600E-mutant melanoma and for BRAF V600-positive Erdheim-Chester disease (FDA.gov). |
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- Simple literal full or partial string matches
- Separate multiple filter terms with a spaces, order doesn't matter (a b c and c b a are equivalent )
- Filtering will only apply to rows that are already loaded on the page, filtering has no impact on query parameters
- Use quotes to match a longer phrase which contains spaces "mtor c1483f"
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| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| BRAF V600E MAP2K1 P387S NRAS A146T | melanoma | resistant | Vemurafenib | Preclinical | Actionable | In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS A146T and MAP2K1 P387S were resistant to Zelboraf (vemurafenib) growth inhibition in culture (PMID: 22389471). | 22389471 |
| BRAF V600E NRAS A146T | melanoma | resistant | Vemurafenib | Preclinical | Actionable | In a preclinical study, melanoma cell lines harboring BRAF V600E and NRAS A146T were resistant to Zelboraf (vemurafenib) growth inhibition in culture (PMID: 22389471). | 22389471 |
| BRAF V600E MAP2K1 K57T | hairy cell leukemia | predicted - resistant | Vemurafenib | Case Reports/Case Series | Actionable | In a clinical case study, a single patient with hairy cell leukemia harboring BRAF V600E, who relapsed after a 38 week remission in response to Zelboraf (vemurafenib) treatment, was found to have acquired multiple clones with Mek/Erk activating mutations, of which the MAP2K1 K57T clone became dominant (PMID: 30341394). | 30341394 |
| BRAF G469R NRAS Q61K | melanoma | resistant | Vemurafenib | Preclinical | Actionable | In a preclinical study, human melanoma cells harboring BRAF G469R and NRAS G61K were insensitive to Zelboraf (vemurafenib) in culture (PMID: 26343583). | 26343583 |
| BRAF V600E | ovary serous adenocarcinoma | predicted - sensitive | Vemurafenib | Case Reports/Case Series | Actionable | In a clinical case study, Zelboraf (vemurafenib) treatment resulted in a partial response lasting more than 21 months in a patient with low grade serous ovarian adenocarcinoma harboring BRAF V600E (PMID: 26490654). | 26490654 |
| BRAF K601N | Advanced Solid Tumor | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Zelboraf (vemurafenib) did not inhibit MEK and ERK activation in transformed cells over expressing the constitutively dimerized BRAF K601N (PMID: 26343582). | 26343582 |
| NRAS G13D | melanoma | resistant | Vemurafenib | Preclinical | Actionable | In a preclinical study, human melanoma cells harboring NRAS G13D were insensitive to Zelboraf (vemurafenib) in culture (PMID: 26343583). | 26343583 |
| BRAF V600E | larynx cancer | predicted - sensitive | 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 |
| NRAS mutant | acute myeloid leukemia | predicted - resistant | Vemurafenib | Preclinical - Patient cell culture | Actionable | In a preclinical study, NRAS mutations correlated with resistance to Zelboraf (vemurafenib) in patient-derived acute myeloid leukemia samples in an ex vivo assay (PMID: 30333627). | 30333627 |
| BRAF wild-type | melanoma | no benefit | Vemurafenib | Preclinical - Patient cell culture | Actionable | In a preclinical study, Zelboraf (vemurafenib) treatment did not inhibit viability of patient-derived wild-type BRAF melanoma cells in culture (PMID: 23715574). | 23715574 |
| BRAF V600E | thyroid gland cancer | conflicting | 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 | 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 CBL dec exp | high grade glioma | predicted - resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, siRNA mediated knockdown of CBL in glioma cell lines harboring BRAF V600E prevented Zelboraf (vemurafenib)-mediated inhibition of cell growth in culture (PMID: 34433654). | 34433654 |
| BRAF V600X | cholangiocarcinoma | sensitive | Vemurafenib | Phase II | Actionable | In a Phase II clinical trial, treatment with Zelboraf (vemurafenib) resulted in partial response in 12% (1/8) and stable disease in 50% (4/8) of cholangiocarcinoma patients with BRAF V600 mutations (PMID: 26287849). | 26287849 |
| NRAS Q61K | neuroblastoma | no benefit | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, neuroblastoma cells with NRAS Q61K showed minimal response to treatment with Zelboraf (vemurafenib) in culture (PMID: 32586982). | 32586982 |
| BRAF F595L | Advanced Solid Tumor | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, treatment with Zelboraf (vemurafenib) did not reduce activation of Mek and Erk by BRAF F595L in transformed cells in culture (PMID: 26582644). | 26582644 |
| BRAF V600E | ganglioglioma | predicted - sensitive | 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 G469L | lung adenocarcinoma | no benefit | Vemurafenib | Case Reports/Case Series | Actionable | In a clinical case study, a lung adenocarcinoma patient harboring BRAF G469L did not respond to Zelboraf (vemurafenib) therapy (PMID: 24035431). | 24035431 |
| BRAF V600X BRAF amp NRAS Q61K | melanoma | resistant | Vemurafenib | Clinical Study - Cohort | Actionable | In a clinical study, a melanoma patient harboring a BRAF V600 mutation developed resistant mutations, BRAF amplification and NRAS Q61K, during treatment with Zelboraf (vemurafenib) (PMID: 24265153). | 24265153 |
| BRAF V600E | salivary gland cancer | predicted - sensitive | 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 MAP2K1 C121S | melanoma | resistant | Vemurafenib | Case Reports/Case Series | Actionable | In a clinical case study, a patient harboring BRAF V600E demonstrated an initial response to treatment with Zelboraf (vemurafenib), but progressed following emergence of a MAP2K1 C121S mutation (PMID: 21383288). | 21383288 |
| BRAF V600E MAP2K1 C121S | melanoma | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, expression of MAP2K1 C121S conferred resistance to Zelboraf (vemurafenib) in melanoma cell lines harboring BRAF V600, resulting in decreased sensitivity to Zelboraf (vemurafenib)-induced inhibition of MAPK pathway activation and cell proliferation in culture (PMID: 24448821). | 24448821 |
| BRAF V600E MAP2K1 C121S | melanoma | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 C121S was resistant to Zelboraf (vemurafenib) in culture (PMID: 28986383). | 28986383 |
| BRAF V600E MAP2K1 D67N | melanoma | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 D67N was resistant to Zelboraf (vemurafenib) in culture (PMID: 28986383). | 28986383 |
| BRAF V600E | Advanced Solid Tumor | sensitive | 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 | Advanced Solid Tumor | sensitive | 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 | high grade glioma | predicted - sensitive | 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 | high grade glioma | predicted - sensitive | 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 MAP2K1 V211D | melanoma | sensitive | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Zelboraf (vemurafenib) inhibited proliferation of melanoma cells harboring BRAF V600E and expressing MAP2K1 V211D in culture (PMID: 28655712). | 28655712 |
| BRAF G466V | lung non-small cell carcinoma | no benefit | Vemurafenib | Case Reports/Case Series | Actionable | In a Phase II trial, Zelboraf (vemurafenib) treatment did not result in response in the cohort of 15 non-small cell lung cancer patients with non-V600 BRAF mutations, which included 3 patients harboring BRAF G466V, and enrollment in this cohort was discontinued (PMID: 31959346; NCT02304809). | 31959346 |
| BRAF G466V | lung non-small cell carcinoma | no benefit | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, non-small cell lung cancer cells harboring BRAF G466V demonstrated decreased sensitivity to Zelboraf (vemurafenib) in culture (PMID: 27523909). | 27523909 |
| BRAF G464E | Advanced Solid Tumor | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Zelboraf (vemurafenib) did not inhibit MEK and ERK activation in transformed cells over expressing the constitutively dimerized BRAF G464E (PMID: 26343582). | 26343582 |
| BRAF V600E | ovarian cancer | predicted - sensitive | 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 | ovarian cancer | predicted - sensitive | 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 | skin melanoma | sensitive | 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 G469A | lung non-small cell carcinoma | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, a non-small cell lung cancer cell line harboring BRAF G469A demonstrated resistance to induction of apoptosis by Zelboraf (vemurafenib,) and treatment with Zelboraf (vemurafenib) was not effective in inhibiting growth in culture (PMID: 25706985). | 25706985 |
| BRAF G469A | lung non-small cell carcinoma | resistant | Vemurafenib | Case Reports/Case Series | Actionable | In a Phase II trial, Zelboraf (vemurafenib) treatment did not result in response in the cohort of 15 non-small cell lung cancer patients with non-V600 BRAF mutations, which included 3 patients harboring BRAF G469A, and enrollment in this cohort was discontinued (PMID: 31959346; NCT02304809). | 31959346 |
| BRAF G606E | Advanced Solid Tumor | no benefit | Vemurafenib | Clinical Study - Cohort | Actionable | In a Phase II trial (MyPathway), Zelboraf (vemurafenib) treatment resulted in an objective response in only 4% (1/23) of patient with advanced solid tumors harboring non-V600 BRAF mutations, 1 of the non-responding patients harbored BRAF G606E (PMID: 29320312; NCT02091141). | 29320312 |
| BRAF N581S | Advanced Solid Tumor | no benefit | Vemurafenib | Clinical Study - Cohort | Actionable | In a Phase II trial (MyPathway), Zelboraf (vemurafenib) treatment resulted in an objective response in only 4% (1/23) of patient with advanced solid tumors harboring non-V600 BRAF mutations, 2 of the non-responding patients harbored BRAF N581S (PMID: 29320312; NCT02091141). | 29320312 |
| BRAF V600E | renal cell carcinoma | predicted - sensitive | 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 |
| NRAS Q61L | melanoma | resistant | Vemurafenib | Preclinical | Actionable | In a preclinical study, human melanoma cells harboring NRAS Q61L were insensitive to Zelboraf (vemurafenib) in culture (PMID: 26343583). | 26343583 |
| BRAF V600K | lung non-small cell carcinoma | predicted - sensitive | Vemurafenib | Case Reports/Case Series | Actionable | In a Phase II trial, Zelboraf (vemurafenib) treatment resulted in a objective response rate of 44.8% (43/96), median duration of response of 6.4 months, median progression-free survival (PFS) of 5.2 months, and median overall survival of 10 months in non-small cell lung cancer patients with BRAF V600 mutations, with a PFS of 2.1 and 6.8 months in the 2 patients harboring BRAF V600K (PMID: 31959346; NCT02304809). | 31959346 |
| BRAF L597V | lung adenocarcinoma | resistant | Vemurafenib | Preclinical - Patient cell culture | Actionable | In a preclinical study, cells derived from a lung adenocarcinoma patient harboring BRAF L597V were resistant to treatment with Zelboraf (vemurafenib) in culture (PMID: 32540409). | 32540409 |
| BRAF K601T | Advanced Solid Tumor | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Zelboraf (vemurafenib) did not inhibit MEK and ERK activation in transformed cells over expressing the constitutively dimerized BRAF K601T (PMID: 26343582). | 26343582 |
| BRAF wild-type NRAS wild-type | melanoma | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, BRAF and NRAS wild-type melanoma cells were resistant to Zelboraf (vemurafenib) in culture (PMID: 27523909). | 27523909 |
| BRAF V600E | thyroid gland anaplastic carcinoma | predicted - sensitive | 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 | thyroid gland Hurthle cell carcinoma | sensitive | 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 | histiocytic and dendritic cell cancer | predicted - sensitive | 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 MERTK over exp | melanoma | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, melanoma cell lines harboring BRAF V600E and overexpression of MERTK were resistant to Zelboraf (vemurafenib) in culture (PMID: 29050198). | 29050198 |
| BRAF G596R | colorectal cancer | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Zelboraf (vemurafenib) did not reduce activation of Erk and Mek in a colorectal cancer cell line harboring BRAF G596R in culture (PMID: 28783719). | 28783719 |
| BRAF V600E MAP2K1 L115P | melanoma | conflicting | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 L115P was resistant to Zelboraf (vemurafenib) in culture (PMID: 28986383). | 28986383 |
| BRAF V600E MAP2K1 L115P | melanoma | conflicting | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Zelboraf (vemurafenib) inhibited proliferation of melanoma cells harboring BRAF V600E and expressing MAP2K1 L115P in culture (PMID: 28655712). | 28655712 |
| BRAF V600E TET2 V1199E | high grade glioma | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, a glioma cell line harboring BRAF V600E developed resistance after prolonged exposure to Zelboraf (vemurafenib) in culture, and was subsequently found to have acquired TET2 V1199E (PMID: 34433654). | 34433654 |
| BRAF L597V NRAS Q61K | lung non-small cell carcinoma | decreased response | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, non-small cell lung cancer cells harboring both BRAF L597V and NRAS Q61K demonstrated decreased sensitivity to Zelboraf (vemurafenib) in culture (PMID: 27523909). | 27523909 |
| BRAF V600E | sarcoma | predicted - sensitive | 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 | cholangiocarcinoma | predicted - sensitive | 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 PDGFRB over exp | melanoma | resistant | Vemurafenib | Preclinical | Actionable | In a preclinical study, over expression of PDGFRB conferred acquired resistance to Zelboraf (vemurafenib) in melanoma cells harboring BRAF V600E in culture (PMID: 21107323). | 21107323 |
| BRAF V600E PDGFRB over exp | melanoma | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600E and overexpressing Pdgfrb demonstrated resistance to Zelboraf (vemurafenib) in culture (PMID: 28986383). | 28986383 |
| BRAF V600E | pleomorphic xanthoastrocytoma | predicted - sensitive | 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 | 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 V47_D380del BRAF V600E | melanoma | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, expression of BRAF V47_D380del in a melanoma cell line harboring BRAF V600E conferred resistance to Zelboraf (vemurafenib) in culture (PMID: 29605720). | 29605720 |
| BRAF T599dup | melanoma | predicted - resistant | Vemurafenib | Case Reports/Case Series | Actionable | In a clinical case study, Zelboraf (vemurafenib) resulted in disease progression in two patients with metastatic melanoma harboring BRAF T599dup (PMID: 35319964). | 35319964 |
| BRAF K601E | colorectal cancer | resistant | Vemurafenib | Preclinical - Pdx | Actionable | In a preclinical study, Zelboraf (vemurafenib) treatment did not inhibit tumor growth in a patient-derived xenograft (PDX) model of colorectal cancer harboring BRAF K601E (PMID: 30559419). | 30559419 |
| BRAF V600E | anaplastic astrocytoma | predicted - sensitive | 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 D594G NRAS G12D | melanoma | decreased response | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, melanoma cells harboring both BRAF D594G and NRAS G12D demonstrated decreased sensitivity to Zelboraf (vemurafenib) in culture (PMID: 27523909). | 27523909 |
| BRAF V600E MAP2K1 F53S | melanoma | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 F53S was resistant to Zelboraf (vemurafenib) in culture (PMID: 28986383). | 28986383 |
| BRAF K601N | lung non-small cell carcinoma | no benefit | Vemurafenib | Case Reports/Case Series | Actionable | In a Phase II trial, Zelboraf (vemurafenib) treatment did not result in response in the cohort of 15 non-small cell lung cancer patients with non-V600 BRAF mutations, which included 2 patients harboring BRAF K601N, and enrollment in this cohort was discontinued (PMID: 31959346; NCT02304809). | 31959346 |
| BRAF L485_P490del | Advanced Solid Tumor | predicted - resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Zelboraf (vemurafenib) failed to inhibit phosphorylation of Mek and Erk in transformed cells expressing BRAF L485_P490del in culture (PMID: 26732095). | 26732095 |
| BRAF V600E | thyroid gland follicular carcinoma | sensitive | 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 MAP2K1 P264L | melanoma | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 P264L was resistant to Zelboraf (vemurafenib) in culture (PMID: 28986383). | 28986383 |
| BRAF V600E NRAS Q61L | melanoma | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing NRAS Q61L demonstrated resistance to Zelboraf (vemurafenib) in culture (PMID: 28986383). | 28986383 |
| BRAF L597R | Advanced Solid Tumor | sensitive | Vemurafenib | Preclinical | Actionable | In a preclinical study, treatment of cells expressing BRAF L597R with the BRAF inhibitor, Zelboraf (vemurafenib), decreased activation of MEK and ERK (PMID: 22798288). | 22798288 |
| BRAF N486_P490del BRAF R509H | Advanced Solid Tumor | resistant | Vemurafenib | Preclinical - Biochemical | Actionable | In a preclinical study, Zelboraf (vemurafenib) failed to reduce Mek phosphorylation in transformed cells expressing BRAF N486_P490del and R509H in culture (PMID: 26996308). | 26996308 |
| BRAF V600E PTEN Y27C | melanoma | predicted - resistant | Vemurafenib | Case Reports/Case Series | Actionable | In a clinical case study, Zelboraf (vemurafenib) treatment in a metastatic melanoma patient harboring BRAF V600E and PTEN Y27C resulted in disease progression after 2.3 months following an initial partial response (PMID: 31980996). | 31980996 |
| BRAF V600E MAP2K1 Y134C | melanoma | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 Y134C was resistant to Zelboraf (vemurafenib) in culture (PMID: 28986383). | 28986383 |
| BRAF K601E | Advanced Solid Tumor | conflicting | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, treatment of cells expressing BRAF K601E with the BRAF inhibitor, Zelboraf (vemurafenib), decreased activation of MEK and ERK (PMID: 22798288). | 22798288 |
| BRAF K601E | Advanced Solid Tumor | conflicting | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Zelboraf (vemurafenib) did not inhibit MEK and ERK activation in transformed cells over expressing the constitutively dimerized BRAF K601E (PMID: 26343582). | 26343582 |
| BRAF K601E | Advanced Solid Tumor | conflicting | Vemurafenib | Clinical Study - Cohort | Actionable | In a Phase II trial (MyPathway), Zelboraf (vemurafenib) treatment resulted in an objective response in only 4% (1/23) of patient with advanced solid tumors harboring non-V600 BRAF mutations, 6 of the non-responding patients harbored BRAF K601E (PMID: 29320312; NCT02091141). | 29320312 |
| BRAF L505H BRAF V600E | melanoma | predicted - resistant | Vemurafenib | Case Reports/Case Series | Actionable | In a clinical case study, a melanoma patient harboring BRAF V600E treated with Zelboraf (vemurafenib) subsequently demonstrated resistance likely due to the secondary resistance mutation, BRAF L505H (PMID: 25515853). | 25515853 |
| BRAF G596R | lung non-small cell carcinoma | no benefit | Vemurafenib | Case Reports/Case Series | Actionable | In a Phase II trial, Zelboraf (vemurafenib) treatment did not result in response in the cohort of 15 non-small cell lung cancer patients with non-V600 BRAF mutations, which included 1 patient harboring BRAF G596R, and enrollment in this cohort was discontinued (PMID: 31959346; NCT02304809). | 31959346 |
| BRAF V600E | salivary gland carcinoma | predicted - sensitive | 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 G464R | Advanced Solid Tumor | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Zelboraf (vemurafenib) did not inhibit MEK and ERK activation in transformed cells over expressing the constitutively dimerized BRAF G464R (PMID: 26343582). | 26343582 |
| BRAF L597S | Advanced Solid Tumor | sensitive | Vemurafenib | Preclinical | Actionable | In a preclinical study, treatment of cells expressing BRAF L597S with the BRAF inhibitor, Zelboraf (vemurafenib), decreased activation of MEK and ERK (PMID: 22798288). | 22798288 |
| BRAF V600E MAP2K1 E203K | melanoma | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 E203K demonstrated resistance to treatment with Zelboraf (vemurafenib) in culture (PMID: 28655712). | 28655712 |
| BRAF V600E MAP2K1 E203K | melanoma | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 E203K was resistant to Zelboraf (vemurafenib) in culture (PMID: 28986383). | 28986383 |
| TP53 D259Y | melanoma | sensitive | Vemurafenib | Preclinical | Actionable | In a preclinical study, Zelboraf (vemurafenib) inhibited proliferation of human melanoma cells TP53 D259Y in culture (PMID: 26343583). | 26343583 |
| BRAF V600E PIK3CA H1047R | colorectal cancer | resistant | Vemurafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Zelboraf (vemurafenib) treatment did not inhibit proliferation of colorectal cancer cells harboring BRAF V600E and PIK3CA H1047R in culture, and did not inhibit tumor growth in a cell line xenograft model (PMID: 22180495). | 22180495 |
| BRAF V487_P492delinsA | pancreatic cancer | resistant | Vemurafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, a human pancreatic cancer cell line harboring BRAF V487_P492delinsA was resistant to treatment with Zelboraf (vemurafenib) in both culture and xenograft models (PMID: 26732095). | 26732095 |
| BRAF V600E MAP2K1 P387S NRAS Q61K NRAS A146T | melanoma | resistant | Vemurafenib | Preclinical | Actionable | In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS Q61K, A146T and MAP2K1 P387S were resistant to Zelboraf (vemurafenib) growth inhibition in culture (PMID: 22389471). | 22389471 |
| BRAF G469V | lung non-small cell carcinoma | no benefit | Vemurafenib | Case Reports/Case Series | Actionable | In a Phase II trial, Zelboraf (vemurafenib) treatment did not result in response in the cohort of 15 non-small cell lung cancer patients with non-V600 BRAF mutations, which included 1 patient harboring BRAF G469V, and enrollment in this cohort was discontinued (PMID: 31959346; NCT02304809). | 31959346 |
| BRAF V600E MAP2K1 K59del | melanoma | resistant | Vemurafenib | Preclinical | Actionable | In a preclinical study, human melanoma cell lines harboring BRAF V600E and MAP2K1 K59del were resistant to Zelboraf (vemurafenib) growth inhibition in culture (PMID: 22389471). | 22389471 |
| BRAF G466A | lung non-small cell carcinoma | no benefit | Vemurafenib | Case Reports/Case Series | Actionable | In a Phase II trial, Zelboraf (vemurafenib) treatment did not result in response in the cohort of 15 non-small cell lung cancer patients with non-V600 BRAF mutations, which included 1 patient harboring BRAF G466A, and enrollment in this cohort was discontinued (PMID: 31959346; NCT02304809). | 31959346 |
| BRAF P731T | Advanced Solid Tumor | no benefit | Vemurafenib | Clinical Study - Cohort | Actionable | In a Phase II trial (MyPathway), Zelboraf (vemurafenib) treatment resulted in an objective response in only 4% (1/23) of patient with advanced solid tumors harboring non-V600 BRAF mutations, 1 of the non-responding patients harbored BRAF P731T (PMID: 29320312; NCT02091141). | 29320312 |
| BRAF V600E MAP2K1 I111N | melanoma | sensitive | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Zelboraf (vemurafenib) inhibited proliferation of melanoma cells harboring BRAF V600E and expressing MAP2K1 I111N in culture (PMID: 28655712). | 28655712 |
| BRAF N486_P490del | melanoma | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Zelboraf (vemurafenib) failed to reduce phosphorylation of Mek and Erk and did not inhibit viability of a melanoma cell line harboring BRAF N486_P490del in culture (PMID: 26996308). | 26996308 |
| BRAF G596R PIK3CA E545K | colorectal cancer | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, colorectal cancer cells harboring BRAF G596R and PIK3CA E545K did not demonstrate sensitivity to Zelboraf (vemurafenib) treatment in culture (PMID: 22180495). | 22180495 |
| BRAF G464V | Advanced Solid Tumor | resistant | Vemurafenib | Clinical Study - Cohort | Actionable | In a Phase II trial (MyPathway), Zelboraf (vemurafenib) treatment resulted in an objective response in only 4% (1/23) of patient with advanced solid tumors harboring non-V600 BRAF mutations, 2 of the non-responding patients harbored BRAF G464V (PMID: 29320312; NCT02091141). | 29320312 |
| BRAF G464V | Advanced Solid Tumor | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Zelboraf (vemurafenib) did not inhibit MEK and ERK activation in transformed cells over expressing the constitutively dimerized BRAF G464V (PMID: 26343582). | 26343582 |
| BRAF K601E | lung non-small cell carcinoma | no benefit | Vemurafenib | Case Reports/Case Series | Actionable | In a Phase II trial, Zelboraf (vemurafenib) treatment did not result in response in the cohort of 15 non-small cell lung cancer patients with non-V600 BRAF mutations, which included 3 patients harboring BRAF K601E, and enrollment in this cohort was discontinued (PMID: 31959346; NCT02304809). | 31959346 |
| BRAF G596R | Advanced Solid Tumor | no benefit | Vemurafenib | Clinical Study - Cohort | Actionable | In a Phase II trial (MyPathway), Zelboraf (vemurafenib) treatment resulted in an objective response in only 4% (1/23) of patient with advanced solid tumors harboring non-V600 BRAF mutations, 1 of the non-responding patients harbored BRAF G596R (PMID: 29320312; NCT02091141). | 29320312 |
| BRAF V600D | melanoma | sensitive | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Zelboraf (vemurafenib) inhibited proliferation of melanoma cells harboring BRAF V600D in culture (PMID: 27523909). | 27523909 |
| BRAF V600X | thyroid gland cancer | predicted - sensitive | Vemurafenib | Phase II | Actionable | In a Phase II clinical trial, treatment with Zelboraf (vemurafenib) resulted in an overall response rate of 29% (2/7), with 1 complete response and 1 partial response, in patients with anaplastic thyroid cancer patients with BRAF V600 mutations (PMID: 26287849). | 26287849 |
| BRAF V600E PIK3CA H1047R PTEN Y68fs | melanoma | predicted - resistant | Vemurafenib | Case Reports/Case Series | Actionable | In a clinical study, a melanoma patient harboring BRAF V600E and PTEN Y68fs treated with Zelboraf (vemurafenib) was found to have acquired PIK3CA H1047R in the post-progression tumor biopsy (PMID: 24265153). | 24265153 |
| BRAF D594N | Advanced Solid Tumor | predicted - resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Zelboraf (vemurafenib) did not reduce activation of Mek in transformed cells expressing BRAF D594N in culture (PMID: 28783719). | 28783719 |
| BRAF N486_P490del BRAF R509H BRAF V600E | Advanced Solid Tumor | resistant | Vemurafenib | Preclinical - Biochemical | Actionable | In a preclinical study, Zelboraf (vemurafenib) failed to reduce Mek phosphorylation in transformed cells expressing BRAF N486_P490del, V600E, and R509H in culture (PMID: 26996308). | 26996308 |
| BRAF K601E | melanoma | no benefit | Vemurafenib | Case Reports/Case Series | Actionable | In a clinical case study, Zelboraf (vemurafenib) treatment resulted in transient disease stabilization followed by metastatic progression in a patient with metastatic melanoma harboring BRAF K601E (PMID: 31182949). | 31182949 |
| BRAF V600E NRAS G12V | melanoma | resistant | Vemurafenib | Preclinical | Actionable | In a preclinical study, expression of NRAS G12V in melanoma cells harboring BRAF V600E conferred resistance to Zelboraf (vemurafenib) in culture (PMID: 26267534). | 26267534 |
| BRAF G466E | melanoma | decreased response | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, melanoma cells harboring BRAF G466E demonstrated decreased sensitivity to Zelboraf (vemurafenib) in culture (PMID: 27523909). | 27523909 |
| BRAF V600X | skin melanoma | sensitive | Vemurafenib | Guideline | Actionable | Zelboraf (vemurafenib) therapy is included in guidelines for patients with unresectable or metastatic cutaneous melanoma harboring BRAF V600 activating mutations, in cases where BRAF/MEK inhibitor combination therapy is contraindicated (NCCN.org). | detail... |
| BRAF V600E | hairy cell leukemia | sensitive | 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 MAP2K1 Q56P | melanoma | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 Q56P demonstrated resistance to treatment with Zelboraf (vemurafenib) in culture (PMID: 28655712). | 28655712 |
| BRAF V600E MAP2K1 Q56P | melanoma | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 Q56P was resistant to Zelboraf (vemurafenib) in culture (PMID: 28986383). | 28986383 |
| BRAF L505H | melanoma | resistant | Vemurafenib | Preclinical | Actionable | In a preclinical study, melanoma cells expressing BRAF L505H were resistant to Zelboraf (vemurafenib) (PMID: 24283590). | 24283590 |
| BRAF N486_P490del | ovarian cancer | resistant | Vemurafenib | Preclinical | Actionable | In a preclinical study, an ovarian cancer cell line harboring BRAF N486_P490del was resistant to Zelboraf (vemurafenib), resulting in minimal inhibition of both cell growth and phosphorylation of MEK and ERK in culture (PMID: 26732095). | 26732095 |
| BRAF N486_P490del | ovarian cancer | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Zelboraf (vemurafenib) failed to reduce phosphorylation of Mek and Erk and did not inhibit viability of an ovarian cancer cell line harboring BRAF N486_P490del in culture (PMID: 26996308). | 26996308 |
| BRAF V600E/K | skin melanoma | sensitive | 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 | neuroendocrine carcinoma | predicted - sensitive | 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 G469A | Advanced Solid Tumor | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Zelboraf (vemurafenib) did not inhibit MEK and ERK activation in transformed cells over expressing the constitutively dimerized BRAF G469A (PMID: 26343582). | 26343582 |
| BRAF G469A | Advanced Solid Tumor | resistant | Vemurafenib | Clinical Study - Cohort | Actionable | In a Phase II trial (MyPathway), Zelboraf (vemurafenib) treatment resulted in an objective response in only 4% (1/23) of patient with advanced solid tumors harboring non-V600 BRAF mutations, 2 of the non-responding patients harbored BRAF G469A (PMID: 29320312; NCT02091141). | 29320312 |
| BRAF V600X | lung non-small cell carcinoma | predicted - sensitive | Vemurafenib | Phase II | Actionable | In a Phase II trial, Zelboraf (vemurafenib) treatment resulted in a objective response rate of 44.8% (43/96), median duration of response of 6.4 months, median progression-free survival of 5.2 months, and median overall survival of 10 months in non-small cell lung cancer patients with BRAF V600 mutations (PMID: 31959346; NCT02304809). | 31959346 |
| BRAF G596V | lung non-small cell carcinoma | predicted - sensitive | Vemurafenib | Case Reports/Case Series | Actionable | In a clinical case study, a non-small cell lung cancer patient harboring BRAF G596V demonstrated a partial response following treatment with Zelboraf (vemurafenib) (PMID: 26200454). | 26200454 |
| MAP2K1 F53C | lymphoma | predicted - resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, expression of MAP2K1 F53C in a lymphoma cell line conferred resistance to inhibition of Erk phosphorylation by Zelboraf (vemurafenib) in culture (PMID: 30341394). | 30341394 |
| BRAF V600X MAP2K1 V60E NRAS T58I NRAS Q61R | melanoma | predicted - resistant | Vemurafenib | Clinical Study - Cohort | Actionable | In a clinical study, a melanoma patient harboring a BRAF V600 mutation developed resistance-associated mutations, MAP2K1 V60E, NRAS T58I, and NRAS Q61R, after 18 weeks of treatment with Zelboraf (vemurafenib) (PMID: 24265153). | 24265153 |
| BRAF L597V | Advanced Solid Tumor | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Zelboraf (vemurafenib) did not inhibit MEK and ERK activation in transformed cells over expressing the constitutively dimerized BRAF L597V (PMID: 26343582). | 26343582 |
| NRAS Q61K | melanoma | resistant | Vemurafenib | Preclinical | Actionable | In a preclinical study, human melanoma cell lines harboring NRAS Q61K were insensitive to Zelboraf (vemurafenib) in culture (PMID: 26343583). | 26343583 |
| NRAS Q61K | melanoma | resistant | Vemurafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, a cell line xenograft model of melanoma harboring NRAS Q61K demonstrated resistance to Zelboraf (vemurafenib) treatment (PMID: 30559419). | 30559419 |
| NRAS mutant | melanoma | resistant | Vemurafenib | Preclinical | Actionable | In a preclinical study, human melanoma cell lines harboring a mutation in NRAS were resistant to Zelboraf (vemurafenib) mediated growth inhibition in culture (PMID: 26343583). | 26343583 |
| BRAF V600E | colorectal cancer | no benefit | 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 | 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 | 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 NRAS Q61K | melanoma | resistant | Vemurafenib | Preclinical | Actionable | In a preclinical study, a NRAS Q61K mutation conferred resistance to Zelboraf (vemurafenib) in melanoma cells harboring BRAF V600E in culture (PMID: 21107323). | 21107323 |
| BRAF V600E NRAS Q61K | melanoma | resistant | Vemurafenib | Case Reports/Case Series | Actionable | In a clinical case study, a melanoma patient harboring BRAF V600E experienced progressive disease after response to treatment Zelboraf (vemurafenib), and was found to have acquired NRAS Q61K (PMID: 34376578). | 34376578 |
| BRAF V600R | melanoma | sensitive | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Zelboraf (vemurafenib) inhibited proliferation of melanoma cells harboring BRAF V600R in culture (PMID: 27523909). | 27523909 |
| BRAF V600M | lung non-small cell carcinoma | predicted - sensitive | Vemurafenib | Case Reports/Case Series | Actionable | In a Phase II trial, Zelboraf (vemurafenib) treatment resulted in a objective response rate of 44.8% (43/96), median duration of response of 6.4 months, median progression-free survival (PFS) of 5.2 months, and median overall survival of 10 months in non-small cell lung cancer patients with BRAF V600 mutations, with a PFS of 5.9 months in the patient harboring BRAF V600M (PMID: 31959346; NCT02304809). | 31959346 |
| BRAF V600E MAP2K1 P387S NRAS Q61K | melanoma | resistant | Vemurafenib | Preclinical | Actionable | In a preclinical study, human melanoma cell lines harboring BRAF V600E, NRAS Q61K and MAP2K1 P387S were resistant to growth inhibition by Zelboraf (vemurafenib) in culture (PMID: 22389471). | 22389471 |
| BRAF V600E PIK3CA E545K | lung non-small cell carcinoma | predicted - sensitive | Vemurafenib | Case Reports/Case Series | Actionable | In a clinical study, Zelboraf (vemurafenib) treatment resulted in stable disease for 6.4 months in a non-small cell lung cancer patient harboring BRAF V600E, tested in tissue and plasma, and PIK3CA E545K, tested in plasma only (PMID: 32859654). | 32859654 |
| BRAF G469V | Advanced Solid Tumor | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Zelboraf (vemurafenib) did not inhibit MEK and ERK activation in transformed cells over expressing the constitutively dimerized BRAF G469V (PMID: 26343582). | 26343582 |
| BRAF V600E | pilocytic astrocytoma | predicted - sensitive | 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 | glioblastoma | predicted - sensitive | 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 | 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 | glioblastoma | predicted - sensitive | 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 L597R | melanoma | predicted - sensitive | Vemurafenib | Case Reports/Case Series | Actionable | In a clinical case study, Zelboraf (vemurafenib) treatment inhibited growth of skin and lung nodules by 30% and resulted in a duration of response of over 4 months in a melanoma patient harboring BRAF L597R, and inhibited Erk activation and reduced viability of melanoma cells derived from the patient in culture (PMID: 23715574). | 23715574 |
| BRAF V600E | IDH-wildtype glioblastoma | predicted - sensitive | Vemurafenib | Case Reports/Case Series | Actionable | In a clinical case study, Zelboraf (vemurafenib) treatment resulted in disease stability over 15 months in a patient with epithelioid glioblastoma harboring BRAF V600E, who previously progressed on conventional treatment options (PMID: 34232949). | 34232949 |
| BRAF V600K | skin melanoma | sensitive | 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 V600K, in cases where BRAF/MEK inhibitor combination therapy is contraindicated (NCCN.org). | detail... |
| BRAF L514V BRAF V600E | melanoma | decreased response | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, melanoma cells expressing BRAF L514V in cis with V600E demonstrated decreased response to Zelboraf (vemurafenib)-induced inhibition of Erk phosphorylation and colony formation compared to cells expressing BRAF V600E in culture (PMID: 29880583). | 29880583 |
| BRAF G466V | colorectal cancer | predicted - resistant | Vemurafenib | Preclinical - Pdx | Actionable | In a preclinical study, Zelboraf (vemurafenib) did not inhibit ERK signaling or tumor growth in a colorectal cancer patient-derived xenograft (PDX) model harboring BRAF G466V, and wild-type RAS and NF1 (PMID: 28783719). | 28783719 |
| BRAF G466V | colorectal cancer | predicted - resistant | Vemurafenib | Preclinical - Pdx | Actionable | In a preclinical study, Zelboraf (vemurafenib) treatment did not inhibit Erk signaling or reduce tumor growth in a patient-derived xenograft (PDX) model of colorectal cancer harboring BRAF G466V (PMID: 30559419). | 30559419 |
| BRAF R509H BRAF V600E | Advanced Solid Tumor | sensitive | Vemurafenib | Preclinical - Biochemical | Actionable | In a preclinical study, Zelboraf (vemurafenib) reduced Mek phosphorylation in transformed cells expressing BRAF V600E and R509H in culture (PMID: 26996308). | 26996308 |
| BRAF V600E | melanoma | sensitive | 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 | 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 G466V | Advanced Solid Tumor | no benefit | Vemurafenib | Clinical Study - Cohort | Actionable | In a Phase II trial (MyPathway), Zelboraf (vemurafenib) treatment resulted in an objective response in only 4% (1/23) of patient with advanced solid tumors harboring non-V600 BRAF mutations, 1 of the non-responding patients harbored BRAF G466V (PMID: 29320312; NCT02091141). | 29320312 |
| BRAF V600X | colorectal cancer | no benefit | Vemurafenib | Phase II | Actionable | In a Phase II clinical trial, treatment with Zelboraf (vemurafenib) in colorectal cancer patients with BRAF V600 mutations did not result in clinical benefit, with no patients achieving response, and 50% (5/10) demonstrating progressive disease (PMID: 26287849). | 26287849 |
| BRAF V600X PTEN H93D | melanoma | predicted - sensitive | Vemurafenib | Clinical Study - Cohort | Actionable | In a clinical study, a melanoma patient harboring a BRAF V600 mutation and PTEN H93D treated with Zelboraf (vemurafenib) for 66 weeks demonstrated a partial response (PMID: 24265153). | 24265153 |
| BRAF V600D | lung non-small cell carcinoma | predicted - sensitive | Vemurafenib | Case Reports/Case Series | Actionable | In a Phase II trial, Zelboraf (vemurafenib) treatment resulted in a objective response rate of 44.8% (43/96), median duration of response of 6.4 months, median progression-free survival (PFS) of 5.2 months, and median overall survival of 10 months in non-small cell lung cancer patients with BRAF V600 mutations, with a PFS of 3.8 months in the patient harboring BRAF V600D (PMID: 31959346; NCT02304809). | 31959346 |
| BRAF V600E FGFR2 A553D | lung non-small cell carcinoma | predicted - sensitive | Vemurafenib | Case Reports/Case Series | Actionable | In a clinical study, Zelboraf (vemurafenib) treatment resulted in stable disease for 3.3 months in a non-small cell lung cancer patient harboring BRAF V600E, tested in tissue and plasma, and FGFR2 A553D, tested in plasma only (PMID: 32859654). | 32859654 |
| BRAF L597Q | Advanced Solid Tumor | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Zelboraf (vemurafenib) did not inhibit MEK and ERK activation in transformed cells over expressing the constitutively dimerized BRAF L597Q (PMID: 26343582). | 26343582 |
| BRAF L597Q | Advanced Solid Tumor | resistant | Vemurafenib | Clinical Study - Cohort | Actionable | In a Phase II trial (MyPathway), Zelboraf (vemurafenib) treatment resulted in an objective response in only 4% (1/23) of patient with advanced solid tumors harboring non-V600 BRAF mutations, 1 of the non-responding patients harbored BRAF L597Q (PMID: 29320312; NCT02091141). | 29320312 |
| BRAF V600E | pancreatic endocrine carcinoma | predicted - sensitive | 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 BRAF over exp | melanoma | resistant | Vemurafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, a cell line xenograft model of melanoma overexpressing BRAF V600E demonstrated resistance to Zelboraf (vemurafenib) treatment (PMID: 30559419). | 30559419 |
| BRAF V504_R506dup | Advanced Solid Tumor | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed human embryonic kidney cells overexpressing Braf V504_R506dup were resistant to Zelboraf (vemurafenib) in culture (PMID: 30575814). | 30575814 |
| BRAF V600E | thyroid gland papillary carcinoma | sensitive | 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 | 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 | 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 N581S | lung non-small cell carcinoma | no benefit | Vemurafenib | Case Reports/Case Series | Actionable | In a Phase II trial, Zelboraf (vemurafenib) treatment did not result in response in the cohort of 15 non-small cell lung cancer patients with non-V600 BRAF mutations, which included 3 patients harboring BRAF N581S, and enrollment in this cohort was discontinued (PMID: 31959346; NCT02304809). | 31959346 |
| BRAF V600E | Erdheim-Chester disease | sensitive | 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.org). | detail... |
| BRAF G469A | lung adenocarcinoma | resistant | Vemurafenib | Preclinical - Patient cell culture | Actionable | In a preclinical study, cells derived from a lung adenocarcinoma patient harboring BRAF G469A were resistant to treatment with Zelboraf (vemurafenib) in culture (PMID: 32540409). | 32540409 |
| BRAF V600E | lung non-small cell carcinoma | sensitive | 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 | 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 | 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 | lung non-small cell carcinoma | sensitive | 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 | 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 MAP2K1 P124L | melanoma | predicted - resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 P124L demonstrated a decreased response to treatment with Zelboraf (vemurafenib) in culture (PMID: 28655712). | 28655712 |
| BRAF V600E MAP2K1 P124L | melanoma | predicted - resistant | Vemurafenib | Case Reports/Case Series | Actionable | In a clinical case study, Zelboraf (vemurafenib) treatment resulted in disease progression within 6 weeks in a metastatic melanoma patient harboring BRAF V600E and MAP2K1 P124L (PMID: 24265153). | 24265153 |
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| Clinical Trial | Phase | Therapies | Title | Recruitment Status | Covered Countries | Other Countries |
|---|---|---|---|---|---|---|
| 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 | ITA | 0 |
| NCT01519323 | Phase I | Vemurafenib | BRIM-P | Terminated | USA | ITA | FRA | ESP | DEU | 5 |
| NCT01667419 | Phase III | Vemurafenib | BRIM8: A Study of Vemurafenib Adjuvant Therapy in Patients With Resected Cutaneous BRAF Mutant Melanoma | Completed | USA | ITA | FRA | ESP | DEU | CAN | BEL | AUT | 21 |
| NCT04801966 | Phase 0 | Palbociclib Alpelisib Atezolizumab Vemurafenib Ribociclib Talazoparib Cobimetinib Trametinib Abemaciclib Dabrafenib Nivolumab Binimetinib Pembrolizumab Encorafenib | Safety and Oversight of the Individually Tailored Treatment Approach: A Novel Pilot Study (TAILOR) | Recruiting | 1 | |
| NCT01767623 | Phase I | Vemurafenib | A Study of The Impact of Severe Hepatic Impairment on the Pharmacokinetics and Safety of Vemurafenib in BRAF V600 Mutation-Positive Cancer Patients | Completed | USA | 6 |
| NCT01748149 | Phase I | Vemurafenib | Vemurafenib in Children With Recurrent/Refractory BRAF Gene V600E (BRAFV600E)-Mutant Gliomas | Active, not recruiting | USA | CAN | 0 |
| NCT01524978 | Phase II | Vemurafenib Cetuximab | A Study of Zelboraf (Vemurafenib) in Patients With BRAF V600 Mutation-Positive Cancers | Completed | USA | FRA | ESP | DEU | 2 |
| NCT02427893 | Phase III | Cobimetinib Vemurafenib | Trial of Vemurafenib and Cobimetinib in Patients With Advanced BRAFV600 Mutant Melanoma | Withdrawn | USA | 0 |
| NCT03220035 | Phase II | Vemurafenib | Pediatric MATCH: Vemurafenib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With BRAF V600 Mutations | Active, not recruiting | USA | 1 |
| NCT01942993 | Phase II | Vemurafenib | The Effects of Treatment With Vemurafenib on the Immune System in Advanced Melanoma | Terminated | USA | 0 |
| NCT02145910 | Phase I | Vemurafenib | Vemurafenib Combined With Whole Brain Radiation Therapy or Radiosurgery in Patients With BRAF Mutation-Positive Melanoma and Brain Metastases | Withdrawn | 0 | |
| NCT01586195 | Phase II | Vemurafenib | Study Of Zelboraf (Vemurafenib) in Patients With Locally-Advanced, Unresectable, Stage IIIc Or Metastatic Melanoma and Activating Exon 15 BRAF Mutations Other Than V600E | Terminated | USA | 0 |
| NCT01781026 | Phase II | Vemurafenib | Phase 2 Study of Neoadjuvant Vemurafenib in Melanoma Patients With Untreated Brain Metastases | Completed | USA | 0 |
| NCT02145143 | Phase 0 | Vemurafenib | Enhancing Radioiodine (RAI) Incorporation Into BRAF Mutant, RAI-Refractory Thyroid Cancers With the BRAF Inhibitor Vemurafenib: A Pilot Study | Active, not recruiting | USA | 0 |
| NCT01909453 | Phase III | Vemurafenib Encorafenib Binimetinib + Encorafenib | Study Comparing Combination of LGX818 Plus MEK162 Versus Vemurafenib and LGX818 Monotherapy in BRAF Mutant Melanoma (COLUMBUS) | Active, not recruiting | USA | ITA | FRA | ESP | DEU | CAN | 23 |
| 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 |
| NCT01711632 | Phase II | Vemurafenib | BRAF Inhibitor, Vemurafenib, in Patients With Relapsed or Refractory Hairy Cell Leukemia | Active, not recruiting | USA | 0 |
| NCT01843738 | Phase I | Vemurafenib | Radiation Use During Vemurafenib Treatment | Withdrawn | USA | 0 |
| NCT01495988 | Phase II | Bevacizumab Vemurafenib | Trial of Vemurafenib With or Without Bevacizumab in Patients With Stage IV BRAFV600 Mutant Melanoma | Terminated | USA | 0 |
| NCT03878524 | Phase I | Oxaliplatin Palbociclib Vemurafenib Sirolimus Tretinoin Celecoxib Ipilimumab Ruxolitinib Dasatinib Abiraterone Idelalisib Trametinib Imatinib Erlotinib Carboplatin Olaparib Panobinostat Bortezomib Afatinib Fluorouracil Vorinostat Pembrolizumab Leucovorin Enzalutamide Ponatinib Nivolumab Everolimus Sunitinib Cabazitaxel Cabozantinib Lenvatinib Pertuzumab Sorafenib Venetoclax Bevacizumab | A Personalized Medicine Study for Patients With Advanced Cancer of the Breast, Prostate, Pancreas or Those With Refractory Acute Myelogenous Leukemia (SMMART) | Recruiting | USA | 0 |
| NCT01739764 | Phase III | Vemurafenib | An Extension (Rollover) Study of Vemurafenib in Patients With BRAF V600 Mutation-Positive Malignancies Previously Enrolled in an Antecedent Vemurafenib Protocol | Completed | USA | ITA | FRA | ESP | DEU | CAN | BEL | 18 |
| NCT02788201 | Phase II | Erlotinib Thiotepa Imatinib Dacarbazine Arsenic trioxide Idarubicin Mitomycin C Thioguanine Mercaptopurine Methotrexate Cladribine Epirubicin Gemcitabine Doxorubicin Bleomycin Etoposide Gefitinib Daunorubicin Lomustine Sorafenib Sunitinib Ifosfamide Asparaginase Ixabepilone Abiraterone Azacitidine Ruxolitinib Decitabine Axitinib Estramustine Floxuridine Lapatinib Carmustine Fludarabine Nilotinib Cisplatin Vismodegib Vandetanib Melphalan Busulfan Carboplatin Toremifene Crizotinib Dactinomycin Temsirolimus Vorinostat Romidepsin Fluorouracil Irinotecan Bortezomib Tamoxifen Topotecan Chlorambucil Pentostatin Eribulin Carfilzomib Vemurafenib Hydroxyurea Exemestane Vincristine Sulfate Dasatinib Mitoxantrone Vinblastine Cytarabine Tretinoin Clofarabine Teniposide Docetaxel Pazopanib Oxaliplatin Streptozocin Paclitaxel Bendamustine Mechlorethamine Mitotane | Genomic Based Assignment of Therapy in Advanced Urothelial Carcinoma | Completed | USA | 0 |
| NCT01813214 | Phase II | Vemurafenib | The Effects of Vemurafenib on Immunity in Patients With Melanoma | Terminated | USA | 0 |
| NCT03155620 | Phase II | Tazemetostat Larotrectinib LY3023414 Vemurafenib Palbociclib Olaparib Ulixertinib Erdafitinib Selumetinib Ensartinib | Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial) | Recruiting | USA | 1 |
| NCT05238831 | Phase II | Vemurafenib Vinorelbine Palbociclib Irinotecan Alpelisib Capecitabine Atezolizumab Paclitaxel Entrectinib Cobimetinib Nab-paclitaxel Fulvestrant Carboplatin Olaparib Pertuzumab/trastuzumab/hyaluronidase-zzxf Niraparib Vismodegib Alectinib Letrozole Ado-trastuzumab emtansine Bevacizumab Eribulin Anastrozole | SMMART Adaptive Clinical Treatment (ACT) Trial | Not yet recruiting | USA | 0 |
| NCT01709292 | Phase II | Vemurafenib | Vemurafenib Neoadjuvant Trial in Locally Advanced Thyroid Cancer | Active, not recruiting | USA | 0 |
| NCT02314481 | Phase II | Vemurafenib Atezolizumab Alectinib Ado-trastuzumab emtansine | Deciphering Antitumour Response and Resistance With INtratumour Heterogeneity (DARWINII) | Recruiting | 1 |
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