Molecular Profile Detail

Profile Name BRAF act mut
Gene Variant Detail

BRAF act mut (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 Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
BRAF act mut non-small cell lung 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 papillary thyroid 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 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 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 Advanced Solid Tumor sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor 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 thyroid 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 melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor 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 thyroid 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 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 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 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
Clinical Trial Phase Therapies Title Recruitment Status
NCT03429803 Phase Ib/II MLN2480 TAK-580 In Gliomas and Other Tumors Recruiting
NCT02012231 Phase Ib/II PLX8394 Phase I/IIa Study to Evaluate the Safety, PK, PD, and Preliminary Efficacy of PLX8394 in Patients With Advanced Cancers. Terminated
NCT02140840 Phase II Trametinib A Phase II Open-Label, Multiple-Dose, Single Agent Study to Evaluate the Overall Response Rate of Orally Administered Trametinib Withdrawn
NCT01596140 Phase I Temsirolimus + Vemurafenib Everolimus + Vemurafenib Vemurafenib in Combination With Everolimus or Temsirolimus With Advanced Cancer Active, not recruiting
NCT03310541 Phase I Capivasertib Capivasertib + Enzalutamide Capivasertib + Fulvestrant AZD5363 in Patients With Advanced Solid Tumors Harboring AKT Mutations Recruiting
NCT03665129 Phase I Durvalumab + IPH5401 IPH5401 (Anti-C5aR) in Combination With Durvalumab in Patients With Advanced Solid Tumors (STELLAR-001) Recruiting
NCT02285439 Phase Ib/II Binimetinib Phase I/II Study of MEK162 for Children With Ras/Raf Pathway Activated Tumors Recruiting
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
NCT03516981 Phase II MK-4280 + Pembrolizumab Lenvatinib + Pembrolizumab A Study of Biomarker-Directed, Pembrolizumab (MK-3475) Based Combination Therapy for Advanced Non-Small Cell Lung Cancer (MK-3475-495) Recruiting
NCT01636622 Phase I Carboplatin + Paclitaxel + Vemurafenib Study of Vemurafenib, Carboplatin, and Paclitaxel Active, not recruiting
NCT02587650 Phase II Ceritinib Capmatinib Regorafenib Entrectinib Capmatinib, Ceritinib, Regorafenib, or Entrectinib in Treating Patients With BRAF/NRAS Wild-Type Stage III-IV Melanoma Completed
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
NCT02949843 Phase II Nivolumab + Pembrolizumab Targeted Therapy in Treating Patients With Incurable Non-Small Cell Lung Cancer With Genetic Mutations Active, not recruiting
NCT02367859 Phase II Dabrafenib + Trametinib Dabrafenib and Trametinib in Treating Patients With BRAF Mutated Ameloblastoma Recruiting
NCT01713972 Phase I Dabrafenib + Pazopanib Dabrafenib and Pazopanib Hydrochloride in Treating Patients With Advanced Malignant Tumors Completed
NCT01765543 Phase I Rifampin + Vemurafenib A Pharmacokinetics Study to Investigate the Effect of Rifampin on Vemurafenib in Patients With BRAFV600 Mutation-Positive Metastatic Malignancy Completed
NCT03114319 Phase I TNO155 Dose Finding Study of TNO155 in Adult Patients With Advanced Solid Tumors Recruiting
NCT03843775 Phase Ib/II Binimetinib + Encorafenib A Study of Binimetinib and Encorafenib in Advanced BRAF Mutant Cancers Recruiting
NCT03088176 Phase I Dabrafenib + Talimogene laherparepvec + Trametinib Combining Talimogene Laherparepvec With BRAF and MEK Inhibitors in BRAF Mutated Advanced Melanoma Recruiting