| 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
|
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
|
melanoma
|
sensitive
|
MLN2480
|
Phase I |
Actionable |
In a Phase I trial, MLN2480 resulted in a median progression free survival of 4.6 months and a partial response in 50% (8/16) of melanoma patients harboring a BRAF mutation (Ann Oncol 2017, Vol 28, Suppl 5, Abstract # 410P; NCT01425008).
|
detail...
|
|
BRAF mutant
|
melanoma
|
sensitive
|
MLN2480
|
Preclinical |
Actionable |
In a preclinical study, MLN2480 demonstrated efficacy in BRAF mutant xenograft models of melanoma and colorectal cancer (J Clin Oncol 31, 2013 (suppl; abstr e13529)).
|
detail...
|
|
BRAF mutant
|
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
|
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
|
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
|
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
|
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
|
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
|
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
|
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
|
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
|
KO-947
|
Preclinical - Pdx |
Actionable |
In a preclinical study, KO-947 inhibited Erk signaling and induced tumor regression in patient-derived xenograft models of BRAF-mutant melanoma (Cancer Res 2017;77(13 Suppl):Abstract nr 5168).
|
detail...
|
|
BRAF mutant
|
thyroid gland cancer
|
sensitive
|
Belvarafenib
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, Belvarafenib (HM95573) inhibited growth of BRAF mutant thyroid cancer cells in culture (Cancer Res 2015;75(15 Suppl):Abstract nr 2607).
|
detail...
|
|
BRAF mutant
|
colorectal cancer
|
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
|
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
|
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
|
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
|
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
|
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
|
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
|
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
|
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
|
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
|
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
|
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
|
Obatoclax
|
Preclinical |
Actionable |
In a preclinical study, obatoclax decreased proliferation in human tumor cell lines with BRAF mutation in culture (PMID: 22460902).
|
22460902
|
|
BRAF mutant
|
melanoma
|
predicted - sensitive
|
ST-162
|
Preclinical - Cell line xenograft |
Actionable |
In a preclinical study, ST-162 treatment resulted in tumor regression in BRAF mutant-melanoma cell line xenograft models (PMID: 28775144).
|
28775144
|
|
BRAF mutant
|
Advanced Solid Tumor
|
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 - 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
|
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
|
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
|
MLN2480
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, MLN2480 inhibited downstream signaling and proliferation of several BRAF mutant solid tumor cell lines in culture (EJC Supp, Nov 2010, Vol 8(7), p40-41).
|
detail...
|
|
BRAF mutant
|
melanoma
|
sensitive
|
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
|
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
|
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
|
sensitive
|
RAF709
|
Phase I |
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
|
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
|
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
|
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
|
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
|
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
|
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
|
thyroid gland cancer
|
predicted - sensitive
|
Selumetinib
|
Phase I |
Actionable |
In a Phase I study, Koselugo (selumetinib) demonstrated an increase in iodine uptake and retention in a subgroup of patients with thyroid cancer that was refractory to radioiodine, including patients with BRAF and NRAS mutations (PMID: 23406027).
|
23406027
|
|
BRAF mutant
|
lung non-small cell carcinoma
|
predicted - sensitive
|
unspecified PD-L1 antibody
|
Clinical Study - Cohort |
Actionable |
In a clinical study, mutant BRAF correlated with prolonged duration on immune checkpoint inhibitor therapy compared to wild-type BRAF in non-small cell lung cancer patients (Ann Oncol 2017, Vol 28, Suppl 5, Abstract #1138PD).
|
detail...
|
|
BRAF mutant
|
Advanced Solid Tumor
|
decreased response
|
XL147
|
Preclinical |
Actionable |
In a preclinical study, tumor cell lines harboring BRAF mutations demonstrated limited sensitivity to XL147 treatment in culture (PMID: 25637314).
|
25637314
|
|
BRAF mutant
|
colorectal cancer
|
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
|
colon cancer
|
predicted - sensitive
|
Selumetinib
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, Selumetinib (AZD6244) resulted in some reduced cell growth in colon cancer cells harboring a BRAF mutation in culture (PMID: 27655129).
|
27655129
|
|
BRAF mutant
|
colorectal cancer
|
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
|
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
|
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
|
melanoma
|
sensitive
|
E6201
|
Preclinical |
Actionable |
In a preclinical study, E6201 inhibited proliferation of several melanoma cell lines in culture and hypersensitivity was associated with BRAF mutations (PMID: 23039341).
|
23039341
|
|
BRAF mutant
|
colorectal cancer
|
sensitive
|
Belvarafenib
|
Preclinical - Cell line xenograft |
Actionable |
In a preclinical study, Belvarafenib (HM95573) inhibited growth of BRAF mutant colorectal cancer cell lines in culture and in cell line xenograft models (Cancer Res 2015;75(15 Suppl):Abstract nr 2607).
|
detail...
|
|
BRAF mutant
|
Advanced Solid Tumor
|
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
|
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
|
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
|
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
|
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
|
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
|
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
|
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
|
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 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
|
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
|
thyroid gland cancer
|
sensitive
|
Dabrafenib
|
Guideline |
Actionable |
Tafinlar (dabrafenib) therapy is included in guidelines for differentiated thyroid carcinoma patients with recurrent, advanced, or metastatic disease harboring BRAF activating mutations, in cases that are not surgically resectable or amenable to radioactive iodine (NCCN.org).
|
detail...
|
|
BRAF act mut
|
thyroid gland cancer
|
sensitive
|
Vemurafenib
|
Guideline |
Actionable |
Zelboraf (vemurafenib) therapy is included in guidelines for differentiated thyroid carcinoma patients with recurrent, advanced, or metastatic disease harboring BRAF activating mutations, in cases that are not surgically resectable or amenable to radioactive iodine (NCCN.org).
|
detail...
|
|
BRAF act mut
|
thyroid gland cancer
|
sensitive
|
Vemurafenib
|
Phase I |
Actionable |
In a Phase I trial, Zelboraf (vemurafenib) demonstrated safety and efficacy in metastatic papillary thyroid cancer patients carrying BRAF activating mutations (PMID: 23489023).
|
23489023
|
|
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
|
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
|
thyroid gland papillary carcinoma
|
sensitive
|
Vemurafenib
|
Phase I |
Actionable |
In a Phase I trial, Zelboraf (vemurafenib) demonstrated safety and efficacy in metastatic papillary thyroid cancer patients carrying BRAF activating mutations (PMID: 23489023).
|
23489023
|
|
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
|
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
|
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
|
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
|