| Molecular Profile |
Indication/Tumor Type |
Response Type |
Therapy Name |
Approval Status |
Evidence Type |
Efficacy Evidence |
References |
|
BRAF mutant
|
Advanced Solid Tumor
|
no benefit
|
LY3009120
|
Case Reports/Case Series |
Actionable |
In a Phase I trial, LY3009120 did not achieve expected pharmacodynamic effects, resulted in stable disease as best overall response in 5 of 12 patients with advanced or metastatic cancer harboring BRAF mutations (PMID: 31645440; NCT02014116).
|
31645440
|
|
BRAF mutant
|
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
|
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
|
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
|
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
|
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
|
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
|
Advanced Solid Tumor
|
predicted - sensitive
|
Binimetinib + Encorafenib
|
Phase II |
Actionable |
In a Phase II trial (BEAVER), Mektovi (binimetinib) and Braftovi (encorafenib) combination therapy demonstrated safety and preliminary efficacy in patients with advanced solid tumors harboring BRAF non-V600E mutations, resulting in an objective response rate of 12.5% (1/8), BRAF mutations including class 1 (n=1), class 2 (n=3), and class 3 (n=5) (J Clin Oncol 39, no. 15_suppl, abstr e15038; NCT03839342).
|
detail...
|
|
BRAF mutant
|
Advanced Solid Tumor
|
predicted - sensitive
|
LXH 254
|
Case Reports/Case Series |
Actionable |
In a Phase I trial, LXH 254 treatment resulted in partial response in 2.6% (2/75) and stable disease in 33% (25/75) of patients with advanced solid tumors harboring MAPK pathway alterations, one of the patient achieved partial response harbored a BRAF mutation (J Clin Oncol 36, no. 15_suppl (May 20 2018) 2586-2586; NCT02607813).
|
detail...
|
|
BRAF mutant
|
lung 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
|
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
|
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
|
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
|
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
|
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
|
thyroid gland cancer
|
predicted - sensitive
|
Selumetinib
|
Phase I |
Actionable |
In a Phase I study, Koselugo (selumetinib) demonstrated an increase in iodine uptake and retention in a subgroup of patients with thyroid cancer that was refractory to radioiodine, including patients with BRAF and NRAS mutations (PMID: 23406027).
|
23406027
|
|
BRAF mutant
|
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
|
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
|
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
|
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
|
Advanced Solid Tumor
|
predicted - sensitive
|
MLN2480
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, MLN2480 inhibited downstream signaling and proliferation of several BRAF mutant solid tumor cell lines in culture (EJC Supp, Nov 2010, Vol 8(7), p40-41).
|
detail...
|
|
BRAF mutant
|
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
|
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
|
lung non-small cell carcinoma
|
predicted - sensitive
|
Dabrafenib + Trametinib
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, treatment with the combination of Mekinist (trametinib) and Tafinlar (dabrafenib) resulted in decreased proliferation and increased apoptosis and enhanced ERK inhibition compared to either agent alone in non-small cell lung cancer cell lines harboring non-BRAF V600 mutations in culture (PMID: 28947956).
|
28947956
|
|
BRAF mutant
|
colorectal cancer
|
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
|
lung non-small cell carcinoma
|
predicted - sensitive
|
unspecified PD-1 antibody
|
Clinical Study - Cohort |
Actionable |
In a clinical study, mutant BRAF correlated with prolonged duration on immune checkpoint inhibitor therapy compared to wild-type BRAF in non-small cell lung cancer patients (Ann Oncol 2017, Vol 28, Suppl 5, Abstract #1138PD).
|
detail...
|
|
BRAF mutant
|
Advanced Solid Tumor
|
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
|
thyroid gland cancer
|
sensitive
|
Belvarafenib
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, Belvarafenib (HM95573) inhibited growth of BRAF mutant thyroid cancer cells in culture (Cancer Res 2015;75(15 Suppl):Abstract nr 2607).
|
detail...
|
|
BRAF mutant
|
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
|
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
|
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
|
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
|
Advanced Solid Tumor
|
sensitive
|
RAF709
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, cancer cell lines harboring BRAF mutations demonstrated increased sensitivity to RAF709 compared to BRAF wild-type cells in culture (PMID: 29343524).
|
29343524
|
|
BRAF mutant
|
Advanced Solid Tumor
|
no benefit
|
Trametinib
|
Phase II |
Actionable |
In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion (n=1) or non-V600 mutations (n=31), resulted in a partial response in 3% (1/32) and stable disease in 31% (10/32) of the patients, with a median progression-free survival of 1.8 months, and a median overall survival of 5.7 months (PMID: 31924734; NCT02465060).
|
31924734
|
|
BRAF mutant
|
melanoma
|
sensitive
|
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
|
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
|
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
|
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
|
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
|
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
|
colon cancer
|
predicted - sensitive
|
Selumetinib
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, Selumetinib (AZD6244) resulted in some reduced cell growth in colon cancer cells harboring a BRAF mutation in culture (PMID: 27655129).
|
27655129
|
|
BRAF mutant
|
melanoma
|
sensitive
|
MLN2480
|
Preclinical |
Actionable |
In a preclinical study, MLN2480 demonstrated efficacy in BRAF mutant xenograft models of melanoma and colorectal cancer (J Clin Oncol 31, 2013 (suppl; abstr e13529)).
|
detail...
|
|
BRAF mutant
|
melanoma
|
sensitive
|
MLN2480
|
Phase I |
Actionable |
In a Phase I trial, MLN2480 resulted in a median progression free survival of 4.6 months and a partial response in 50% (8/16) of melanoma patients harboring a BRAF mutation (Ann Oncol 2017, Vol 28, Suppl 5, Abstract # 410P; NCT01425008).
|
detail...
|
|
BRAF mutant
|
colorectal cancer
|
sensitive
|
MLN2480
|
Preclinical |
Actionable |
In a preclinical study, MLN2480 demonstrated efficacy in BRAF mutant xenograft models of melanoma and colorectal cancer (J Clin Oncol 31, 2013 (suppl; abstr e13529)).
|
detail...
|
|
BRAF mutant
|
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
|
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
|
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
|
splenic marginal zone lymphoma
|
not applicable
|
N/A
|
Guideline |
Diagnostic |
BRAF mutations aid in the diagnosis of splenic marginal zone lymphoma (NCCN.org).
|
detail...
|
|
BRAF mutant
|
melanoma
|
predicted - sensitive
|
UNC2025 + Vemurafenib
|
Preclinical - Pdx & cell culture |
Actionable |
In a preclinical study, the combination therapy of UNC2025 and Zelboraf (vemurafenib) resulted in greater inhibition of colony formation and apoptotic induction in melanoma cells harboring a BRAF mutation in culture and led to a higher degree of tumor growth inhibition in a patient derived xenograft (PDX) model of melanoma with a BRAF mutation when compared to either therapy alone (PMID: 30482852).
|
30482852
|
|
BRAF mutant
|
colorectal cancer
|
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
|
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
|
colorectal cancer
|
predicted - sensitive
|
LSN3074753
|
Preclinical - Pdx |
Actionable |
In a preclinical study, LSN3074753 resulted in a disease control rate of 8.3% (1/12) in BRAF mutant patient-derived xenograft models of colorectal cancer (PMID: 28611205).
|
28611205
|
|
BRAF mutant
|
melanoma
|
sensitive
|
PLX8394
|
Preclinical |
Actionable |
In a preclinical study, PLX8394 blocked survival and growth of vemurafenib/PLX4720-resistant melanoma cells harboring BRAF V600E splice variants in culture (PMID: 24422853).
|
24422853
|
|
BRAF mutant
|
pancreatic adenocarcinoma
|
sensitive
|
Trametinib
|
Preclinical |
Actionable |
In a preclinical study, Mekinist (trametinib) inhibited growth of human pancreatic adenocarcinoma cells harboring mutant BRAF in culture (PMID: 26343583).
|
26343583
|
|
BRAF mutant
|
melanoma
|
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
|
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 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
|
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
|
stomach carcinoma
|
predicted - sensitive
|
KO-947
|
Preclinical - Pdx |
Actionable |
In a preclinical study, KO-947 inhibited Erk signaling and induced tumor regression in patient-derived xenograft models of BRAF-mutant gastric carcinoma (Cancer Res 2017;77(13 Suppl):Abstract nr 5168).
|
detail...
|
|
BRAF mutant
|
melanoma
|
sensitive
|
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
|
melanoma
|
predicted - sensitive
|
Ulixertinib
|
Phase I |
Actionable |
In a Phase I trial, treatment with BVD-523 (ulixertinib) resulted in a best response of stable disease in six melanoma patients and a partial response in three melanoma patients all harboring a BRAF mutation (PMID: 29247021).
|
29247021
|
|
BRAF mutant
|
melanoma
|
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
|
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
|
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
|
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 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 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 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
|
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
|
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
|
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 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 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
|