Molecular Profile Detail

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Profile Name BRAF G464E
Gene Variant Detail

BRAF G464E (gain of function)

Relevant Treatment Approaches MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LY3009120

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
BRAF act mut melanoma no benefit Sorafenib Phase II Actionable In a Phase II study, Nexavar (sorafenib) displayed negligible efficacy in melanoma patients with BRAF mutations (PMID: 16880785, PMID: 22394203). 22394203 16880785
BRAF act mut melanoma sensitive Cobimetinib Preclinical - Cell line xenograft Actionable In a preclinical study, Cobimetinib (GDC-0973) induced cell death in human melanoma cell lines harboring BRAF activating mutations in culture and inhibited tumor growth in xenograft models (PMID: 22084396). 22084396
BRAF mutant Advanced Solid Tumor sensitive Dabrafenib Phase I Actionable In a Phase I clinical trial, Tafinlar (dabrafenib) demonstrated safety and efficacy in patients with BRAF V600E positive solid tumors (PMID: 22608338). 22608338
BRAF mutant melanoma sensitive Selumetinib Case Reports/Case Series Actionable In a Phase II trial, 5 out of 6 patients with advanced melanoma exhibiting a response to Koselugo (selumetinib) had BRAF-mutant tumors (PMID: 22048237). 22048237
BRAF act mut Advanced Solid Tumor sensitive Binimetinib + Encorafenib Phase Ib/II Actionable In a Phase Ib/II trial, Binimetinib (MEK162), in combination with Encorafenib (LGX818), demonstrated safety and efficacy in patients with BRAF mutant advanced solid tumors (J Clin Oncol 31, 2013 (suppl; abstr 9029)). detail...
BRAF act mut Advanced Solid Tumor sensitive PLX8394 Preclinical Actionable In a preclinical study, PLX8394 had been shown to block survival and growth of vemurafenib/PLX4720-resistant cells harboring distinct BRAF activating mutations (PMID: 24422853). 24422853
BRAF mutant thyroid cancer predicted - sensitive Selumetinib Phase I Actionable In a Phase I study, Koselugo (selumetinib) demonstrated an increase in iodine uptake and retention in a subgroup of patients with thyroid cancer that was refractory to radioiodine, including patients with BRAF and NRAS mutations (PMID: 23406027). 23406027
BRAF mutant colorectal cancer sensitive Tovorafenib Preclinical - Cell line xenograft Actionable In a preclinical study, Tovorafenib (MLN2480) demonstrated efficacy in BRAF mutant xenograft models of melanoma and colorectal cancer (J Clin Oncol 31, 2013 (suppl; abstr e13529)). detail...
BRAF mutant melanoma sensitive Tovorafenib Preclinical - Cell line xenograft Actionable In a preclinical study, Tovorafenib (MLN2480) demonstrated efficacy in BRAF mutant xenograft models of melanoma and colorectal cancer (J Clin Oncol 31, 2013 (suppl; abstr e13529)). detail...
BRAF mutant Advanced Solid Tumor sensitive Obatoclax Preclinical Actionable In a preclinical study, obatoclax decreased proliferation in human tumor cell lines with BRAF mutation in culture (PMID: 22460902). 22460902
BRAF mutant melanoma sensitive PLX8394 Preclinical Actionable In a preclinical study, PLX8394 blocked survival and growth of vemurafenib/PLX4720-resistant melanoma cells harboring BRAF V600E splice variants in culture (PMID: 24422853). 24422853
BRAF mutant melanoma sensitive Tubastatin A Preclinical Actionable In a preclinical study, Tubastatin A inhibited proliferation of BRAF mutant melanoma cell lines in culture (PMID: 25957812). 25957812
BRAF mutant melanoma sensitive E6201 Preclinical Actionable In a preclinical study, E6201 inhibited proliferation of several melanoma cell lines in culture and hypersensitivity was associated with BRAF mutations (PMID: 23039341). 23039341
BRAF mutant melanoma sensitive E6201 + LY294002 Preclinical Actionable In a preclinical study, E6201 and LY294002 synergistically inhibited proliferation of melanoma cell lines harboring BRAF mutations in culture, regardless of PTEN mutation status (PMID: 23039341). 23039341
BRAF mutant melanoma sensitive Vemurafenib + Voruciclib Phase I Actionable In a Phase I trial, Voruciclib (P1446A-05) and Zelboraf (vemurafenib) combination therapy demonstrated safety and preliminary efficacy, resulted in complete response in 33% (1/3) and partial response in 67% (2/3) of BRAFi-naïve melanoma patients harboring BRAF mutations (J Clin Oncol 33, 2015 (suppl; abstr 9076)). detail...
BRAF mutant Advanced Solid Tumor decreased response XL147 Preclinical Actionable In a preclinical study, tumor cell lines harboring BRAF mutations demonstrated limited sensitivity to XL147 treatment in culture (PMID: 25637314). 25637314
BRAF mutant multiple myeloma sensitive Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of human multiple myeloma cells harboring mutant BRAF in culture (PMID: 26343583). 26343583
BRAF mutant lung adenocarcinoma sensitive Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of lung adenocarcinoma cells harboring mutant BRAF in culture (PMID: 26343583). 26343583
BRAF mutant pancreatic adenocarcinoma sensitive Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of human pancreatic adenocarcinoma cells harboring mutant BRAF in culture (PMID: 26343583). 26343583
BRAF mutant colorectal cancer resistant Trametinib Preclinical Actionable In a preclinical study, a majority of human colorectal cancer cell lines (4/7) harboring mutant BRAF were insensitive to Mekinist (trametinib) in culture (PMID: 26343583). 26343583
BRAF mutant colorectal cancer sensitive Alpelisib + Cetuximab + Encorafenib Phase Ib/II Actionable In a Phase Ib/II trial, the triple combination therapy of Encorafenib (LGX818), Erbitux (cetuximab), and Alpelisib (BYL719) resulted in an overall response rate of 18% (5/28), including 5 patients with a partial response, and led to a median progression free survival of 4.2 months and response duration of 12 weeks (PMID: 28363909). detail... 28363909
BRAF mutant melanoma predicted - sensitive BI-847325 Preclinical - Cell line xenograft Actionable In a preclinical study, treatment with BI-847325 resulted in decreased expression of Mcl-1 and Mek, and inhibited growth of BRAF-mutant melanoma cell lines in culture, and inhibited tumor growth melanoma cell line xenograft models harboring BRAF mutations, including models with BRAF inhibitor resistance (PMID: 25873592). 25873592
BRAF mutant melanoma sensitive Palbociclib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring a BRAF mutation demonstrated greater sensitivity to the combination treatment of Mekinist (trametinib) and Ibrance (palbociclib) in culture when compared to either agent alone (PMID: 27488531). 27488531
BRAF mutant colorectal cancer decreased response PLX4720 Preclinical - Cell culture Actionable In a preclinical study, BRAF mutant colorectal cancer cell lines demonstrated reduced sensitivity to PLX4720 in culture (PMID: 26351322). 26351322
BRAF mutant colorectal cancer sensitive AZ628 + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, Koselugo (selumetinib) and AZ628 synergistically inhibited Mapk signaling and cell proliferation in BRAF mutant colorectal cancer cell lines in culture (PMID: 26351322). 26351322
BRAF mutant melanoma sensitive S63845 + Trametinib Preclinical - Cell culture Actionable In a preclinical study, combination of S63845 and Mekinist (trametinib) resulted in potent cytotoxic effects in BRAF-mutated melanoma cells in culture compared to the cytostatic effect of Mekinist (trametinib) alone (PMID: 27760111). 27760111
BRAF mutant melanoma sensitive S63845 + Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, combination of S63845 and Zelboraf (vemurafenib) resulted in potent cytotoxic effects in BRAF-mutated melanoma cells in culture compared to the cytostatic effect of Zelboraf (vemurafenib) alone (PMID: 27760111). 27760111
BRAF mutant Advanced Solid Tumor predicted - sensitive Tovorafenib Preclinical - Cell culture Actionable In a preclinical study, Tovorafenib (MLN2480) inhibited downstream signaling and proliferation of several BRAF mutant solid tumor cell lines in culture (EJC Supp, Nov 2010, Vol 8(7), p40-41). detail...
BRAF mutant lung non-small cell carcinoma predicted - sensitive Dabrafenib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, treatment with the combination of Mekinist (trametinib) and Tafinlar (dabrafenib) resulted in decreased proliferation and increased apoptosis and enhanced ERK inhibition compared to either agent alone in non-small cell lung cancer cell lines harboring non-BRAF V600 mutations in culture (PMID: 28947956). 28947956
BRAF mutant colon cancer predicted - sensitive Selumetinib Preclinical - Cell culture Actionable In a preclinical study, Selumetinib (AZD6244) resulted in some reduced cell growth in colon cancer cells harboring a BRAF mutation in culture (PMID: 27655129). 27655129
BRAF act mut colorectal cancer predicted - sensitive VX-11e + WEHI-539 Preclinical - Cell culture Actionable In a preclinical study, inhibition of Erk signaling by VX-11e sensitized colorectal cancer cell lines harboring KRAS or BRAF activating mutations to WEHI-539 in culture (PMID: 27974663). 27974663
BRAF act mut colorectal cancer no benefit Venetoclax + VX-11e Preclinical - Cell culture Actionable In a preclinical study, inhibition of Erk signaling by VX-11e did not sensitize colorectal cancer cell lines harboring KRAS or BRAF activating mutations to Venclexta (venetoclax) in culture (PMID: 27974663). 27974663
BRAF mutant melanoma sensitive Binimetinib + Buparlisib Preclinical - Cell culture Actionable In a preclinical study, the combination of Binimetinib (MEK162) and Buparlisib (BKM120) resulted in improved cell growth inhibition compared to either agent alone in a metastatic melanoma cell line harboring a BRAF mutation in culture (PMID: 27307593). 27307593
BRAF mutant melanoma sensitive Buparlisib + Encorafenib Preclinical - Cell culture Actionable In a preclinical study, the combination of Buparlisib (BKM120) and Encorafenib (LGX818) resulted in improved cell growth inhibition compared to either agent alone in a metastatic melanoma cell line harboring a BRAF mutation in culture (PMID: 27307593). 27307593
BRAF mutant melanoma sensitive Buparlisib Preclinical - Cell line xenograft Actionable In a preclinical study, Buparlisib (BKM120) treatment in human melanoma cell line xenograft models with brain metastases and harboring a BRAF mutation resulted in inhibition of brain tumor growth (PMID: 27307593). 27307593
BRAF mutant Advanced Solid Tumor predicted - sensitive PF-00477736 + PF3644022 Preclinical - Cell line xenograft Actionable In a preclinical study, Chk1 inhibitor PF-477736 and MK2 inhibitor PF3644022 synergistically inhibited growth of various cancer cell lines harboring BRAF mutations in culture and in cell line xenograft models (PMID: 26140595). 26140595
BRAF mutant colon cancer predicted - sensitive PF-00477736 + PF3644022 Preclinical - Cell line xenograft Actionable In a preclinical study, Chk1 inhibitor PF-477736 and MK2 inhibitor PF3644022 synergistically inhibited tumor growth in cell line xenograft models of BRAF mutant colon cancer (PMID: 26140595). 26140595
BRAF mutant colorectal cancer predicted - sensitive Binimetinib Phase I Actionable In a Phase I trial, Binimetinib (MEK162) treatment resulted in an estimated progression free survival of 1.4 months and overall survival of 7.1 months in colorectal cancer patients harboring BRAF mutations (PMID: 28152546). 28152546
BRAF mutant Advanced Solid Tumor predicted - sensitive KO-947 Preclinical - Pdx Actionable In a preclinical study, KO-947 resulted in tumor regression in patient derived xenograft (PDX) models harboring either a BRAF mutation, NRAS mutation, or KRAS mutation (EJC Dec 2016, 69:1; S126). detail...
BRAF mutant Advanced Solid Tumor no benefit CC-90003 Phase I Actionable In a Phase Ia trial, CC-90003 treatment did not result in any objective responses and demonstrated toxicity in advanced solid tumor patients harboring KRAS, NRAS, or BRAF mutations (AJ Clin Oncol 35, 2017 (suppl; abstr 2577)). detail...
BRAF mutant colorectal cancer sensitive Cetuximab + Encorafenib Phase Ib/II Actionable In a Phase Ib/II trial, the combination therapy of Erbitux (cetuximab) and Encorafenib (LGX818) in colorectal cancer patients harboring a BRAF mutation resulted in an overall response rate of 19% (5/26), including 1 patient with a complete response and 4 patients with a partial response, and led to a median progression free survival of 3.7 months and response duration of 46 weeks (PMID: 28363909). 28363909
BRAF mutant melanoma sensitive PET-16 + Vemurafenib Preclinical - Cell line xenograft Actionable In a preclinical study, PET-16 and Zelboraf (vemurafenib) synergistically inhibited growth of melanoma cell lines in culture, resulted in enhanced tumor growth inhibition in cell ine xenograft models (PMID: 26984758). 26984758
BRAF mutant melanoma predicted - sensitive KO-947 Preclinical - Pdx Actionable In a preclinical study, KO-947 inhibited Erk signaling and induced tumor regression in patient-derived xenograft models of BRAF-mutant melanoma (Cancer Res 2017;77(13 Suppl):Abstract nr 5168). detail...
BRAF mutant lung non-small cell carcinoma predicted - sensitive KO-947 Preclinical - Pdx Actionable In a preclinical study, KO-947 inhibited Erk signaling and induced tumor regression in patient-derived xenograft models of BRAF-mutant non-small cell lung cancer harboring (Cancer Res 2017;77(13 Suppl):Abstract nr 5168). detail...
BRAF mutant pancreatic cancer predicted - sensitive KO-947 Preclinical - Pdx Actionable In a preclinical study, KO-947 inhibited Erk signaling and induced tumor regression in patient-derived xenograft models of BRAF-mutant pancreatic cancer (Cancer Res 2017;77(13 Suppl):Abstract nr 5168). detail...
BRAF mutant colorectal cancer predicted - sensitive KO-947 Preclinical - Pdx Actionable In a preclinical study, KO-947 inhibited Erk signaling and induced tumor regression in patient-derived xenograft models of BRAF-mutant colorectal cancer (Cancer Res 2017;77(13 Suppl):Abstract nr 5168). detail...
BRAF mutant stomach carcinoma predicted - sensitive KO-947 Preclinical - Pdx Actionable In a preclinical study, KO-947 inhibited Erk signaling and induced tumor regression in patient-derived xenograft models of BRAF-mutant gastric carcinoma (Cancer Res 2017;77(13 Suppl):Abstract nr 5168). detail...
BRAF mutant cervix carcinoma predicted - sensitive KO-947 Preclinical - Pdx Actionable In a preclinical study, KO-947 inhibited Erk signaling and induced tumor regression in patient-derived xenograft models of BRAF-mutant cervical carcinoma (Cancer Res 2017;77(13 Suppl):Abstract nr 5168). detail...
BRAF mutant colorectal cancer predicted - sensitive Dabrafenib + Panitumumab + Trametinib Phase Ib/II Actionable In a Phase I/II trial, treatment with the triple combination of Tafinlar (dabrafenib), Mekinist (trametinib), and Vectibix (panitumumab) resulted in an objective response rate (ORR) of 21% and median progression-free survival (mPFS) of 4.2 mo, compared with 0% ORR and mPFS of 2.6 mo with Mekinist (trametinib) plus Vectibix (panitumumab), and 10% ORR and mPFS of 3.5 mo with Tafinlar (dabrafenib) plus Vectibix (panitumumab) in patients with BRAF-mutant colorectal cancer (PMID: 27770002; NCT01750918). 27770002
BRAF mutant lung non-small cell carcinoma predicted - sensitive unspecified PD-1 antibody Clinical Study - Cohort Actionable In a clinical study, mutant BRAF correlated with prolonged duration on immune checkpoint inhibitor therapy compared to wild-type BRAF in non-small cell lung cancer patients (Ann Oncol 2017, Vol 28, Suppl 5, Abstract #1138PD). detail...
BRAF mutant melanoma sensitive Encorafenib Phase I Actionable In a Phase I trial, Encorafenib (LGX818) treatment resulted in an overall response rate (ORR) of 60% (15/25) and a median progression-free survival (mPFS) of 12.4 months in BRAF inhibitor-naïve melanoma patients harboring BRAF mutations, and an ORR of 22% (6/29) and mPFS of 1.9 months in BRAF inhibitor-pretreated patients (PMID: 28611198; NCT01436656). 28611198
BRAF mutant colorectal cancer predicted - sensitive LSN3074753 Preclinical - Pdx Actionable In a preclinical study, LSN3074753 resulted in a disease control rate of 8.3% (1/12) in BRAF mutant patient-derived xenograft models of colorectal cancer (PMID: 28611205). 28611205
BRAF mutant colorectal cancer sensitive Cetuximab + LSN3074753 Preclinical - Pdx Actionable In a preclinical study, LSN3074753 and Erbitux (cetuximab) synergistically inhibited tumor growth in patient-derived xenograft models of colorectal cancer harboring BRAF mutations, resulted in a disease control rate of 41.7% (5/12) (PMID: 28611205). 28611205
BRAF mutant melanoma predicted - sensitive ST-162 Preclinical - Cell line xenograft Actionable In a preclinical study, ST-162 treatment resulted in tumor regression in BRAF mutant-melanoma cell line xenograft models (PMID: 28775144). 28775144
BRAF mutant melanoma predicted - sensitive Ulixertinib Case Reports/Case Series Actionable In a Phase I trial, treatment with Ulixertinib (BVD-523) resulted in a best response of stable disease in six melanoma patients and a partial response in three melanoma patients all harboring a BRAF mutation (PMID: 29247021; NCT01781429). 29247021
BRAF mutant colorectal cancer predicted - resistant SYM004 Preclinical - Pdx Actionable In a preclinical study, patient-derived xenograft (PDX) models of colorectal cancer harboring KRAS, NRAS or BRAF mutations demonstrated poor response to SYM004 treatment compared to wild-type models (PMID: 29423521). 29423521
BRAF mutant Advanced Solid Tumor sensitive RAF709 Preclinical - Cell culture Actionable In a preclinical study, cancer cell lines harboring BRAF mutations demonstrated increased sensitivity to RAF709 compared to BRAF wild-type cells in culture (PMID: 29343524). 29343524
BRAF act mut lung non-small cell carcinoma sensitive RAF709 Preclinical - Pdx Actionable In a preclinical study, RAF709 inhibited tumor growth in patient-derived xenograft (PDX) models of non-small cell lung cancer harboring BRAF activating mutations (PMID: 29343524). 29343524
BRAF mutant colorectal cancer sensitive Belvarafenib Preclinical - Cell line xenograft Actionable In a preclinical study, Belvarafenib (HM95573) inhibited growth of BRAF mutant colorectal cancer cell lines in culture and in cell line xenograft models (Cancer Res 2015;75(15 Suppl):Abstract nr 2607). detail...
BRAF mutant thyroid cancer sensitive Belvarafenib Preclinical - Cell culture Actionable In a preclinical study, Belvarafenib (HM95573) inhibited growth of BRAF mutant thyroid cancer cells in culture (Cancer Res 2015;75(15 Suppl):Abstract nr 2607). detail...
BRAF mutant colorectal cancer no benefit Regorafenib Phase II Actionable In a Phase II clinical trial (PREVIUM), Stivarga (regorafenib) treatment resulted in 0% (0/15) 6-month progression free survival (PFS), a 2.2-month median PFS, and a median overall survival of 3.3 months in metastatic colorectal cancer patients with KRAS (n=9), NRAS (n=3) or BRAF (n=2) mutations who failed first line therapy; however, the trial was terminated early due to poor accrual (PMID: 30120161; NCT02175654). 30120161
BRAF mutant lung non-small cell carcinoma predicted - sensitive unspecified PD-L1 antibody Clinical Study - Cohort Actionable In a clinical study, mutant BRAF correlated with prolonged duration on immune checkpoint inhibitor therapy compared to wild-type BRAF in non-small cell lung cancer patients (Ann Oncol 2017, Vol 28, Suppl 5, Abstract #1138PD). detail...
BRAF mutant melanoma predicted - sensitive Belvarafenib Phase I Actionable In Phase I trials, Belvarafenib (HM95573) treatment resulted in partial response in a patients with BRAF-mutant melanoma in a dose escalation study, and partial response in 33% (2/6) of BRAF-mutant melanoma patients in a dose expansion study (J Clin Oncol 37, 2019 (suppl; abstr 3000); NCT02405065, NCT03118817). detail...
BRAF mutant Advanced Solid Tumor predicted - sensitive LXH 254 Case Reports/Case Series Actionable In a Phase I trial, LXH 254 treatment resulted in partial response in 2.6% (2/75) and stable disease in 33% (25/75) of patients with advanced solid tumors harboring MAPK pathway alterations, one of the patient achieved partial response harbored a BRAF mutation (J Clin Oncol 36, no. 15_suppl (May 20 2018) 2586-2586; NCT02607813). detail...
BRAF mutant splenic marginal zone lymphoma not applicable N/A Guideline Diagnostic BRAF mutations aid in the diagnosis of splenic marginal zone lymphoma (NCCN.org). detail...
BRAF mutant Advanced Solid Tumor no benefit LY3009120 Case Reports/Case Series Actionable In a Phase I trial, LY3009120 did not achieve expected pharmacodynamic effects, resulted in stable disease as best overall response in 5 of 12 patients with advanced or metastatic cancer harboring BRAF mutations (PMID: 31645440; NCT02014116). 31645440
BRAF act mut lung non-small cell carcinoma predicted - resistant Osimertinib Case Reports/Case Series Actionable In a retrospective analysis, activating BRAF mutations were identified in 4 of 100 patients with non-small cell lung cancer at treatment discontinuation of Tagrisso (osimertinib) (PMID: 31839416). 31839416
BRAF mutant melanoma predicted - sensitive UNC2025 + Vemurafenib Preclinical - Pdx & cell culture Actionable In a preclinical study, the combination therapy of UNC2025 and Zelboraf (vemurafenib) resulted in greater inhibition of colony formation and apoptotic induction in melanoma cells harboring a BRAF mutation in culture and led to a higher degree of tumor growth inhibition in a patient derived xenograft (PDX) model of melanoma with a BRAF mutation when compared to either therapy alone (PMID: 30482852). 30482852
BRAF mutant Advanced Solid Tumor no benefit Trametinib Phase II Actionable In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion (n=1) or non-V600 mutations (n=31), resulted in a partial response in 3% (1/32) and stable disease in 31% (10/32) of the patients, with a median progression-free survival of 1.8 months, and a median overall survival of 5.7 months (PMID: 31924734; NCT02465060). 31924734
BRAF mutant lymphoma no benefit Trametinib Phase II Actionable In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion (n=1) or non-V600 mutations (n=31), resulted in a partial response in 3% (1/32) and stable disease in 31% (10/32) of the patients, with a median progression-free survival of 1.8 months, and a median overall survival of 5.7 months (PMID: 31924734; NCT02465060). 31924734
BRAF mutant colorectal cancer predicted - sensitive SY-5609 Preclinical - Pdx Actionable In a preclinical study, SY-5609 treatment resulted in 90% or more tumor growth inhibition or tumor regression in 50% (5/10) of patient-derived xenograft (PDX) models of colorectal cancer harboring BRAF mutations (J Clin Oncol 38: 2020 (suppl; abstr 3585)). detail...
BRAF mutant lung non-small cell carcinoma unknown unspecified immune checkpoint inhibitor Clinical Study Actionable In a retrospective clinical study, no significant difference in overall survival (19.0 vs 18.4 months) was found in patients with non-small cell lung cancer harboring BRAF V600E (n=14), amplification (n=5), or non-V600E mutations (n=12) who received immunotherapy compared to those who never received immunotherapy (PMID: 31367539). 31367539
BRAF mutant lung non-small cell carcinoma unknown unspecified immune checkpoint inhibitor Clinical Study - Cohort Actionable In a retrospective clinical study, patients with non-small cell lung cancer harboring rare targetable drivers (RTD) (BRAF, ERBB2/3, RET, MET, ROS1, NTRK) who received immune checkpoint inhibitors (ICI) achieved longer median overall survival (mOS) (32 vs 13 mo, p=0.01) compared to those who did not receive ICI, mOS was not reached in patients harboring BRAF non-V600E (n=5) mutations, although RTD type was not associated with OS in a univariate analysis (PMID: 30268448). 30268448
BRAF mutant Advanced Solid Tumor predicted - sensitive Binimetinib + Encorafenib Phase II Actionable In a Phase II trial (BEAVER), Mektovi (binimetinib) and Braftovi (encorafenib) combination therapy demonstrated safety and preliminary efficacy in advanced solid tumor patients harboring BRAF non-V600E mutations including class 1 (n=1), class 2 (n=4), and class 3 (n=5), with an objective response rate of 22% (2/9) and a partial response in a patient with ampullary cancer harboring BRAF D594G and an unconfirmed PR in a melanoma patient harboring BRAF G469S (Annals of Oncology 32 (2021): S596; NCT03839342). detail...
BRAF act mut Advanced Solid Tumor predicted - sensitive CC-91516 Preclinical - Patient cell culture Actionable In a preclinical study, CC-91516 treatment induced apoptosis and inhibited viability of cancer cells harboring BRAF activating mutations, and inhibited ex vivo colony formation from patient-derived xenograft (PDX) models in culture (Cancer Res 2022;82(12_Suppl):Abstract nr 1180). detail...
BRAF act mut colorectal cancer predicted - sensitive CC-91516 Preclinical - Biochemical Actionable In a preclinical study, CC-91516 inhibited Mapk signaling in BRAF-mutant colorectal cancer cells (Cancer Res 2022;82(12_Suppl):Abstract nr 1180). detail...
BRAF act mut melanoma predicted - sensitive Ipilimumab + Nivolumab Clinical Study Actionable In a systematic review, an analysis of several clinical trials demonstrated Opdivo (nivolumab) plus Yervoy (ipilimumab) resulted in improved overall survival (OS) compared to BRAF plus MEK inhibitor in BRAF-mutant advanced melanoma patients when considering the entire study period, and analysis of the period beginning 12 months after treatment initiation demonstrated significantly greater OS and progression-free survival (PMID: 33556898; NCT01844505, NCT01584648, NCT01597908, NCT01909453, NCT01689519). 33556898
BRAF act mut colorectal cancer sensitive BCA101 Preclinical - Cell line xenograft Actionable In a preclinical study, treatment with BCA101 resulted in a tumor growth inhibition of 31% compared to 8% with Erbitux (cetuximab) in a BRAF-mutant colorectal cancer cell line and human peripheral blood mononuclear cells coimplantation xenograft model (PMID: 37074042). 37074042
BRAF mutant melanoma sensitive Tovorafenib Phase I Actionable In a Phase I trial, Tovorafenib (MLN2480) treatment resulted in stable disease in 23% (5/22) of patients with advanced solid tumors in the dose escalation phase, an objective response rate of 15% (10/68) in the dose expansion phase with responses in 50% (8/16) of patients with RAF and MEK inhibitor-naive BRAF-mutant melanoma, an overall median duration of response of 6.0 months, and a median progression-free survival of 1.9 months (PMID: 37219686; NCT01425008). 37219686