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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) 28 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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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
BRAF V600E MAP2K1 S331R melanoma sensitive Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 S331R in culture (PMID: 36442478). 36442478
BRAF V600E MAP2K1 S212N melanoma sensitive Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 S212N in culture (PMID: 36442478). 36442478
BRAF V600E ovarian serous cystadenocarcinoma predicted - sensitive Vemurafenib Case Reports/Case Series Actionable In a clinical case study, Zelboraf (vemurafenib) treatment resulted in a complete radiological response that lasted for 3 years in a patient with low-grade serous cystadenocarcinoma of the ovary harboring BRAF V600E (PMID: 36967525). 36967525
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 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 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 V600E MAP2K1 E203K colon adenocarcinoma resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, a colon adenocarcinoma cell line harboring BRAF V600E and expressing MAP2K1 E203K was resistant to Zelboraf (vemurafenib) in culture (PMID: 36442478). 36442478
BRAF V600E MAP2K1 S150F melanoma sensitive Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 S150F in culture (PMID: 36442478). 36442478
BRAF del exon4-8 BRAF V600E melanoma predicted - resistant Vemurafenib Case Reports/Case Series Actionable In a clinical case study, a deletion of BRAF exons 4-8 was identified in the post-progression biopsy of a melanoma patient harboring BRAF V600E who was treated with Zelboraf (vemurafenib) (PMID: 22113612). 22113612
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 V600E MAP2K1 F53Y melanoma resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 F53Y was resistant to Zelboraf (vemurafenib) in culture (PMID: 36442478). 36442478
BRAF V600X cholangiocarcinoma predicted - sensitive Vemurafenib Case Reports/Case Series Actionable In a Phase II 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; NCT01524978). 26287849
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 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 MAP2K1 I103_K104del melanoma resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 I103_K104del was resistant to Zelboraf (vemurafenib) in culture (PMID: 36442478). 36442478
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
BRAF V600E MAP2K1 L63_D67del melanoma sensitive Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 L63_D67del in culture (PMID: 36442478). 36442478
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 G128D colon adenocarcinoma resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, a colon adenocarcinoma cell line harboring BRAF V600E and expressing MAP2K1 G128D was resistant to Zelboraf (vemurafenib) in culture (PMID: 36442478). 36442478
BRAF V600E MAP2K1 R349K melanoma sensitive Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 R349K in culture (PMID: 36442478). 36442478
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 V600E MAP2K1 Q58* melanoma sensitive Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 Q58* in culture (PMID: 36442478). 36442478
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 V60E melanoma resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 V60E was resistant to Zelboraf (vemurafenib) in culture (PMID: 36442478). 36442478
BRAF V600E MAP2K1 E203V melanoma resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 E203V was resistant to Zelboraf (vemurafenib) in culture (PMID: 36442478). 36442478
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 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
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 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 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 Guideline Actionable Zelboraf (vemurafenib) is included in guidelines as a first-line therapy for advanced or metastatic non-small cell lung cancer patients harboring BRAF V600E mutations who can not tolerate the combination of Mekinist (trametinib) and Tafinlar (dabrafenib) (NCCN.org). detail...
BRAF V600E lung non-small cell carcinoma sensitive 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
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
SMARCA4 mut TP53 mut adrenal gland cancer resistant Vemurafenib Preclinical Actionable In a preclinical study, human adrenal gland cancer cells harboring SMARCA4 and TP53 mutations were resistant to Zelboraf (vemurafenib) mediated growth inhibition in culture (PMID: 26343583). 26343583
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 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 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 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 V600E MAP2K1 R49H melanoma sensitive Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 R49H in culture (PMID: 36442478). 36442478
BRAF V600E MAP2K1 N345T melanoma sensitive Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 N345T in culture (PMID: 36442478). 36442478
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 L505H Advanced Solid Tumor predicted - resistant Vemurafenib Preclinical - Biochemical Actionable In a preclinical study, cells expressing BRAF L505H were resistant to treatment with Zelboraf (vemurafenib) in culture (PMID: 34108213). 34108213
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 Preclinical - Cell line xenograft Actionable In a preclinical study, colorectal cancer cell lines harboring BRAF V600E 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 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 MAP2K1 K57E melanoma resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 K57E was resistant to Zelboraf (vemurafenib) in culture (PMID: 36442478). 36442478
BRAF del exon2-8 BRAF V600E melanoma predicted - resistant Vemurafenib Case Reports/Case Series Actionable In a clinical case study, a deletion of BRAF exons 2-8 was identified in the post-progression biopsy of a melanoma patient harboring BRAF V600E who was treated with Zelboraf (vemurafenib) (PMID: 22113612). 22113612
BRAF V600E MAP2K1 N382H melanoma sensitive Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 N382H in culture (PMID: 36442478). 36442478
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 MAP2K1 D136N melanoma sensitive Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 D136N in culture (PMID: 36442478). 36442478
BRAF V600E MAP2K1 D336H melanoma sensitive Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 D336H in culture (PMID: 36442478). 36442478
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 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
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 NRAS Q61K papillary thyroid carcinoma predicted - resistant Vemurafenib Case Reports/Case Series Actionable In a clinical case study, NRAS Q61K was identified on post-progression biopsy in a patient with metastatic papillary thyroid carcinoma harboring BRAF V600E, who previously responded to Zelboraf (vemurafenib) treatment (PMID: 30036146). 30036146
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 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 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 V600E MAP2K1 A132V melanoma sensitive Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 A132V in culture (PMID: 36442478). 36442478
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: 36442478). 36442478
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
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 P293S melanoma sensitive Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 P293S in culture (PMID: 36442478). 36442478
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 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 S327T melanoma sensitive Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 S327T in culture (PMID: 36442478). 36442478
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 L485_P490delinsF Advanced Solid Tumor predicted - resistant Vemurafenib Preclinical - Biochemical Actionable In a preclinical study, Zelboraf (vemurafenib) did not inhibit Mek and Erk phosphorylation in cells expressing BRAF L485_P490delinsF in culture (PMID: 37656784). 37656784
BRAF V600E MAP2K1 F53C melanoma resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 F53C was resistant to Zelboraf (vemurafenib) in culture (PMID: 36442478). 36442478
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 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 V600E high grade glioma sensitive Vemurafenib Guideline Actionable Zelboraf (vemurafenib) is included in guidelines as adjuvant therapy for pediatric patients with diffuse high-grade gliomas harboring BRAF V600E, or as a preferred regimen for patients with recurrent or progressive disease (NCCN.org). detail...
BRAF V600E high grade glioma 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 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
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 MAP2K1 K4N melanoma sensitive Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 K4N in culture (PMID: 36442478). 36442478
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
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 V487_P492delinsA Advanced Solid Tumor predicted - resistant Vemurafenib Preclinical - Biochemical Actionable In a preclinical study, Zelboraf (vemurafenib) did not inhibit Mek and Erk phosphorylation in cells expressing BRAF V487_P492delinsA in culture (PMID: 37656784). 37656784
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 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 V600X lung non-small cell carcinoma predicted - sensitive Vemurafenib Case Reports/Case Series Actionable In a Phase II trial, treatment with Zelboraf (vemurafenib) resulted in an overall response rate of 42% (8/19, 8 partial responses) in patients with non-small cell lung cancer harboring BRAF V600 mutations, with a median progression-free survival of 7.3 months (PMID: 26287849; NCT01524978}. 26287849
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 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 V600E MAP2K1 R108Q melanoma sensitive Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 R108Q in culture (PMID: 36442478). 36442478
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 L485_P490delinsFS Advanced Solid Tumor predicted - resistant Vemurafenib Preclinical - Biochemical Actionable In a preclinical study, Zelboraf (vemurafenib) did not inhibit Mek and Erk phosphorylation in cells expressing BRAF L485_P490delinsFS in culture (PMID: 37656784). 37656784
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 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 R506_K507insLLR Advanced Solid Tumor resistant Vemurafenib Preclinical - Cell line xenograft Actionable In a preclinical study, cells expressing BRAF R506_K507insLLR were resistant to treatment with Zelboraf (vemurafenib) in culture and cell line xenograft models (PMID: 34108213). 34108213
BRAF V600E MAP2K1 I99_K104del melanoma resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 I99_K104del was resistant to Zelboraf (vemurafenib) in culture (PMID: 36442478). 36442478
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 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
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 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
BRAF V600E anaplastic thyroid carcinoma predicted - sensitive Vemurafenib Case Reports/Case Series Actionable In a clinical case study, first-line adjuvant therapy with Zelboraf (vemurafenib) resulted in a partial remission of the tumor and lymphatic and pulmonary metastases after 36 days of treatment in a patient with analplastic thyroid carcinoma harboring BRAF V600E, with a near-complete regression observed within 5 months of treatment initiation (PMID: 36855200). 36855200
BRAF V600E anaplastic thyroid 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 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 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 V600E, 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 I310L melanoma sensitive Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 I310L in culture (PMID: 36442478). 36442478
BRAF V504_R506dup Advanced Solid Tumor resistant Vemurafenib Preclinical - Cell line xenograft Actionable In a preclinical study, cells expressing BRAF V504_R506dup were resistant to treatment with Zelboraf (vemurafenib) in culture and cell line xenograft models (PMID: 34108213). 34108213
BRAF V504_R506dup Advanced Solid Tumor resistant Vemurafenib Preclinical - Biochemical Actionable In a preclinical study, transformed cells overexpressing BRAF V504_R506dup were resistant to Zelboraf (vemurafenib) in culture (PMID: 30575814). 30575814
BRAF V600E MAP2K1 S86A melanoma sensitive Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 S86A in culture (PMID: 36442478). 36442478
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 V600E triple-receptor negative breast cancer predicted - sensitive Vemurafenib Case Reports/Case Series Actionable In a clinical case study, Zelboraf (vemurafenib) treatment resulted in a partial response in the lung lesion lasting at least 19 months in a patient with metastatic triple-negative breast cancer harboring BRAF V600E (PMID: 33976643). 33976643
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 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 V600X colorectal cancer no benefit Vemurafenib Case Reports/Case Series Actionable In a Phase II 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; NCT01524978). 26287849
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 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 V600E MAP2K1 F53V melanoma resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 F53V was resistant to Zelboraf (vemurafenib) in culture (PMID: 36442478). 36442478
BRAF V600E MAP2K1 G79V melanoma sensitive Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 G79V in culture (PMID: 36442478). 36442478
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 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 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 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 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 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 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 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 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 V600E MAP2K1 R201H melanoma sensitive Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 R201H in culture (PMID: 36442478). 36442478
BRAF V600E ameloblastoma sensitive Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) inhibited viability of an ameloblastoma cell line harboring BRAF V600E in culture (PMID: 24859340). 24859340
BRAF V600E ameloblastoma sensitive Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) inhibited viability of ameloblastoma cell lines harboring BRAF V600E in culture (PMID: 35689405). 35689405
BRAF V600E MAP2K1 Q58_E62del melanoma resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 Q58_E62del was resistant to Zelboraf (vemurafenib) in culture (PMID: 36442478). 36442478
BRAF V600E MAP2K1 L215F melanoma sensitive Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 L215F in culture (PMID: 36442478). 36442478
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 hairy cell leukemia sensitive Vemurafenib Case Reports/Case Series Actionable In a clinical case study, Zelboraf (vemurafenib) treatment resulted in complete resolution of the brain lesions after 3 months of treatment, decreased spleen size, and resolution of leukemic retinopathy in a patient with hairy cell leukemia harboring BRAF V600E (PMID: 36713531). 36713531
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 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 MAP2K1 P105_A106del melanoma resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 P105_A106del was resistant to Zelboraf (vemurafenib) in culture (PMID: 36442478). 36442478
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
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 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 V600E follicular thyroid 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 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 MAP2K1 S231L melanoma sensitive Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 S231L in culture (PMID: 36442478). 36442478
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 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 V600E MAP2K1 P306H melanoma sensitive Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 P306H in culture (PMID: 36442478). 36442478
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 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 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 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 V600E MAP2K1 P326H melanoma sensitive Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 P326H in culture (PMID: 36442478). 36442478
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 MAP2K1 L115P melanoma conflicting Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) inhibited viability in a melanoma cell line harboring BRAF V600E and expressing MAP2K1 L115P in culture (PMID: 36442478). 36442478
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 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 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 V600E MAP2K1 G128D melanoma resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 G128D was resistant to Zelboraf (vemurafenib) in culture (PMID: 36442478). 36442478
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 V600E childhood pilocytic astrocytoma predicted - sensitive Vemurafenib Case Reports/Case Series Actionable In a clinical case study, Zelboraf (vemurafenib) treatment resulted in a partial response in a pediatric patient with pilocytic astrocytoma harboring BRAF V600E (PMID: 38976815). 38976815
BRAF V600E synovial sarcoma predicted - sensitive Vemurafenib Case Reports/Case Series Actionable In a clinical case study, Zelboraf (vemurafenib) resulted in a partial response after 4 months of treatment in a patient with intrathoracic synovial sarcoma harboring SS18-SSX1 (e10:e6) and BRAF V600E (PMID: 37417899). 37417899
BRAF V600E MAP2K1 P162S melanoma sensitive Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 P162S in culture (PMID: 36442478). 36442478
BRAF V600E MAP2K1 G294E melanoma sensitive Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 G294E in culture (PMID: 36442478). 36442478
BRAF V600X thyroid cancer predicted - sensitive Vemurafenib Case Reports/Case Series Actionable In a Phase II 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; NCT01524978). 26287849
BRAF N486_P490del Advanced Solid Tumor predicted - resistant Vemurafenib Preclinical - Biochemical Actionable In a preclinical study, Zelboraf (vemurafenib) did not inhibit Mek and Erk phosphorylation in cells expressing BRAF N486_P490del in culture (PMID: 37656784). 37656784
BRAF V600E thyroid 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 thyroid 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 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
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 MAP2K1 Q56_G61delinsR melanoma resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 Q56_G61delinsR was resistant to Zelboraf (vemurafenib) in culture (PMID: 36442478). 36442478
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 MAP2K1 V127M melanoma sensitive Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 V127M in culture (PMID: 36442478). 36442478
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 V600E MAP2K1 R201C melanoma sensitive Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 R201C in culture (PMID: 36442478). 36442478
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 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 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 D67N colon adenocarcinoma resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, a colon adenocarcinoma cell line harboring BRAF V600E and expressing MAP2K1 D67N was resistant to Zelboraf (vemurafenib) in culture (PMID: 36442478). 36442478
BRAF V600E histiocytosis predicted - sensitive Vemurafenib Case Reports/Case Series Actionable In a clinical study, Zelboraf (vemurafenib) treatment resulted in complete remission in 2 pediatric patients with Langerhans cell histiocytosis harboring BRAF V600E (PMID: 39190425). 39190425
BRAF V487_P492delinsA pancreatic cancer resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, a pancreatic cancer cell line harboring BRAF V487_P492delinsA was resistant to Zelboraf (vemurafenib) in culture (PMID: 37164118). 37164118
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 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 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 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 MAP2K1 Y229H melanoma sensitive Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 Y229H in culture (PMID: 36442478). 36442478
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 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 papillary thyroid carcinoma sensitive Vemurafenib Case Reports/Case Series Actionable In a clinical case study, Zelboraf (vemurafenib) treatment resulted in a partial response with approximately 90% tumor shrinkage and a progression-free survival of 10 months in a patient with metastatic papillary thyroid carcinoma harboring BRAF V600E (PMID: 38489728). 38489728
BRAF V600E papillary thyroid 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 papillary thyroid 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 papillary thyroid 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 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
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 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: 36442478). 36442478
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 del exon2-10 BRAF V600E melanoma predicted - resistant Vemurafenib Case Reports/Case Series Actionable In a clinical case study, a deletion of BRAF exons 2-10 was identified in the post-progression biopsy of three melanoma patients harboring BRAF V600E who were treated with Zelboraf (vemurafenib) (PMID: 22113612). 22113612
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 V600E MAP2K1 K57T melanoma resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 K57T was resistant to Zelboraf (vemurafenib) in culture (PMID: 36442478). 36442478
BRAF V600E MAP2K1 F53_Q58delinsL melanoma resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 F53_Q58delinsL was resistant to Zelboraf (vemurafenib) in culture (PMID: 36442478). 36442478
BRAF V600E MAP2K1 E102_I103del melanoma resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 E102_I103del was resistant to Zelboraf (vemurafenib) in culture (PMID: 36442478). 36442478
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
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 V600E MAP2K1 L235H melanoma sensitive Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 L235H in culture (PMID: 36442478). 36442478
BRAF V600E MAP2K1 W247* melanoma sensitive Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 W247* in culture (PMID: 36442478). 36442478
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 V600E MAP2K1 V93F melanoma sensitive Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 V93F in culture (PMID: 36442478). 36442478
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 V600E MAP2K1 S72G melanoma sensitive Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 S72G in culture (PMID: 36442478). 36442478
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 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 V600E MAP2K1 V154I melanoma sensitive Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 V154I in culture (PMID: 36442478). 36442478
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 V600E MAP2K1 F53I melanoma resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 F53I was resistant to Zelboraf (vemurafenib) in culture (PMID: 36442478). 36442478
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 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 del exon4-10 BRAF V600E melanoma predicted - resistant Vemurafenib Case Reports/Case Series Actionable In a clinical case study, a deletion of BRAF exons 4-10 was identified in the post-progression biopsy of a melanoma patient harboring BRAF V600E who was treated with Zelboraf (vemurafenib) (PMID: 22113612). 22113612
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 V600E MAP2K1 M146I melanoma sensitive Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 M146I in culture (PMID: 36442478). 36442478
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 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 MAP2K1 V258I melanoma sensitive Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 V258I in culture (PMID: 36442478). 36442478
BRAF L485_P490delinsY Advanced Solid Tumor predicted - resistant Vemurafenib Preclinical - Biochemical Actionable In a preclinical study, Zelboraf (vemurafenib) did not inhibit Mek and Erk phosphorylation in cells expressing BRAF L485_P490delinsY in culture (PMID: 37656784). 37656784
BRAF V600E MAP2K1 A76V melanoma sensitive Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 A76V in culture (PMID: 36442478). 36442478
BRAF V600E MAP2K1 V224M melanoma sensitive Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 V224M in culture (PMID: 36442478). 36442478
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 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 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 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 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 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 V600E MAP2K1 K57N melanoma resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 K57N was resistant to Zelboraf (vemurafenib) in culture (PMID: 36442478). 36442478
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 G469R NRAS Q61K melanoma resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, human melanoma cells harboring BRAF G469R and NRAS Q61K were insensitive to Zelboraf (vemurafenib) in culture (PMID: 26343583). 26343583
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 V600E MAP2K1 G176S melanoma sensitive Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 G176S in culture (PMID: 36442478). 36442478
BRAF V600E ovarian cancer predicted - sensitive Vemurafenib Case Reports/Case Series Actionable In a Phase II trial (VE-BASKET), responses were seen in ovarian cancer patients harboring BRAF V600E (n=4) when treated with Zelboraf (vemurafenib), including 2 patients with a partial response (PMID: 32029534; NCT01524978). 32029534
BRAF V600E ovarian cancer predicted - sensitive 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 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 V600E MAP2K1 F53L melanoma resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 F53L was resistant to Zelboraf (vemurafenib) in culture (PMID: 36442478). 36442478
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 L485F Advanced Solid Tumor predicted - resistant Vemurafenib Preclinical - Biochemical Actionable In a preclinical study, cells expressing BRAF L485F were resistant to treatment with Zelboraf (vemurafenib) in culture (PMID: 34108213). 34108213
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 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 V600E MAP2K1 I103N melanoma resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 I103N was resistant to Zelboraf (vemurafenib) in culture (PMID: 36442478). 36442478
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 P124S melanoma resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 P124S was resistant to Zelboraf (vemurafenib) in culture (PMID: 36442478). 36442478
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 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 MAP2K1 P124S colon adenocarcinoma resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, a colon adenocarcinoma cell line harboring BRAF V600E and expressing MAP2K1 P124S was resistant to Zelboraf (vemurafenib) in culture (PMID: 36442478). 36442478
BRAF V600E oncocytic carcinoma of the thyroid 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 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 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 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 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 V600E MAP2K1 P264S melanoma sensitive Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 P264S in culture (PMID: 36442478). 36442478
BRAF V600E MAP2K1 R291K melanoma sensitive Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 R291K in culture (PMID: 36442478). 36442478
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 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
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

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Clinical Trial Phase Therapies Title Recruitment Status Covered Countries Other Countries
NCT01781026 Phase II Vemurafenib Phase 2 Study of Neoadjuvant Vemurafenib in Melanoma Patients With Untreated Brain Metastases Completed USA 0
NCT01524978 Phase II Vemurafenib Cetuximab A Study of Zelboraf (Vemurafenib) in Patients With BRAF V600 Mutation-Positive Cancers Completed USA | GBR | FRA | ESP | DEU 1
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
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 Withdrawn 0
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) Terminated AUS 0
NCT01709292 Phase II Vemurafenib Vemurafenib Neoadjuvant Trial in Locally Advanced Thyroid Cancer Active, not 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 | ROU | NZL | NLD | ITA | ISR | HUN | HRV | GRC | GBR | FRA | ESP | DEU | CYP | CAN | BRA | BEL 8
NCT01942993 Phase II Vemurafenib The Effects of Treatment With Vemurafenib on the Immune System in Advanced Melanoma Terminated USA 0
NCT02427893 Phase III Cobimetinib Vemurafenib Trial of Vemurafenib and Cobimetinib in Patients With Advanced BRAFV600 Mutant Melanoma Withdrawn USA 0
NCT01843738 Phase I Vemurafenib Radiation Use During Vemurafenib Treatment Withdrawn USA 0
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 | TUR | ISR | GRC | GBR | AUS 1
NCT03220035 Phase II Vemurafenib Vemurafenib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With BRAF V600 Mutations (A Pediatric MATCH Treatment Trial) Active, not recruiting USA 1
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
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 | CAN | AUS 1
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) Active, not recruiting ITA 0
NCT01667419 Phase III Vemurafenib BRIM8: A Study of Vemurafenib Adjuvant Therapy in Patients With Resected Cutaneous BRAF Mutant Melanoma Completed USA | SWE | POL | NZL | NOR | NLD | ITA | ISR | IRL | HRV | GBR | FRA | EST | ESP | DEU | CZE | CHE | CAN | BRA | BEL | AUT | AUS | ARG 6
NCT01711632 Phase II Vemurafenib BRAF Inhibitor, Vemurafenib, in Patients With Relapsed or Refractory Hairy Cell Leukemia Completed USA 0
NCT01748149 Phase I Vemurafenib Vemurafenib in Children With Recurrent/Refractory BRAF Gene V600E (BRAFV600E)-Mutant Gliomas Active, not recruiting USA | CAN 0
NCT01813214 Phase II Vemurafenib The Effects of Vemurafenib on Immunity in Patients With Melanoma Terminated 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
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
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) Terminated USA 0
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
NCT01909453 Phase III Vemurafenib Encorafenib Binimetinib + Encorafenib Study Comparing Combination of LGX818 Plus MEK162 Versus Vemurafenib and LGX818 Monotherapy in BRAF Mutant Melanoma (COLUMBUS) Completed USA | TUR | SWE | SVK | POL | NOR | NLD | ITA | ISR | HUN | GRC | GBR | FRA | ESP | DEU | CZE | CHE | CAN | BRA | AUS | ARG 8
NCT01519323 Phase I Vemurafenib BRIM-P Terminated USA | SVK | POL | ITA | ISR | GBR | FRA | ESP | DEU | AUS 0
NCT01659151 Phase II Aldesleukin Fludarabine Vemurafenib Vemurafenib With Lymphodepletion Plus Adoptive Cell Transfer and High Dose IL-2 Metastatic Melanoma Active, not recruiting USA 0
NCT05159245 Phase II Vemurafenib Tepotinib Vismodegib Apalutamide Alectinib Regorafenib Entrectinib Pertuzumab + Trastuzumab Pemigatinib Atezolizumab Cobimetinib Dabrafenib + Trametinib Dabrafenib Trametinib Abemaciclib The Finnish National Study to Facilitate Patient Access to Targeted Anti-cancer Drugs (FINPROVE) Recruiting FIN 0
NCT02314481 Phase II Vemurafenib Atezolizumab Alectinib Ado-trastuzumab emtansine Deciphering Antitumour Response and Resistance With INtratumour Heterogeneity (DARWINII) Active, not recruiting GBR 0


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