Molecular Profile Detail

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Profile Name BRAF wild-type
Gene Variant Detail

BRAF wild-type (no effect)

Relevant Treatment Approaches

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Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
BRAF wild-type high grade glioma predicted - sensitive Everolimus + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, Afinitor (everolimus) and Selumetinib (AZD6244) synergistically inhibited growth and induced apoptosis in glioma cell lines in culture (PMID: 27217440). 27217440
BRAF wild-type melanoma resistant PLX4720 Preclinical - Cell line xenograft Actionable In a preclinical study, PLX4720 did not inhibit growth of BRAF wild-type melanoma cells in culture or in cell line xenograft models (PMID: 18287029). 18287029
BRAF wild-type melanoma sensitive Trametinib Phase I Actionable In a Phase I study, 10% (4/39) of wild-type BRAF melanoma patients had a partial response to Mekinist (trametinib) (PMID: 22805292; NCT00687622). 22805292
BRAF wild-type melanoma predicted - sensitive RAF265 Preclinical Actionable In a preclinical study, RAF265 inhibited the growth of melanoma tumors orthotopically implanted in mice, including tumors wild-type for BRAF (PMID: 22351689). 22351689
BRAF wild-type melanoma predicted - sensitive RAF265 Phase I Actionable In a Phase I trial, treatment with RAF265 in melanoma patients resulted in an objective response rate of 12.1% (8/66), including a partial response in four patients harboring BRAF V600E, two partial responses and one complete response in patients with wild-type BRAF, and one complete response in a patient with unknown mutational status (PMID: 28719152). 28719152
BRAF wild-type Advanced Solid Tumor resistant BGB-283 Preclinical - Cell culture Actionable In a preclinical study, a variety of BRAF wild-type tumor cell lines were insensitive to BGB-283 in culture (PMID: 26208524). 26208524
BRAF wild-type melanoma no benefit Selumetinib Phase II Actionable In a Phase II trial, a favorable response rate to Koselugo (selumetinib) was observed in BRAF-mutant, but not BRAF wild-type, melanoma patients (PMID: 22048237). 22048237
BRAF wild-type melanoma sensitive Palbociclib Preclinical - Cell culture Actionable In a preclinical study, BRAF wild-type melanoma cells demonstrated decreased cell viability when treated with Ibrance (palbociclib) in culture (PMID: 27488531). 27488531
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 wild-type melanoma decreased response Palbociclib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, a BRAF wild-type melanoma cell line demonstrated minimal sensitivity when treated with the combination of Ibrance (palbociclib) and Mekinist (trametinib) in culture (PMID: 27488531). 27488531
BRAF wild-type thyroid gland cancer sensitive CLM3 Preclinical Actionable In a preclinical study, CLM3 inhibited growth, Egfr signaling, and CCND1 expression, in BRAF wild-type thyroid cancer cells in culture (PMID: 24423321). 24423321
BRAF wild-type lung non-small cell carcinoma resistant GDC0879 Preclinical - Pdx & cell culture Actionable In a preclinical study, GDC0879 failed to inhibit growth of BRAF wild-type non-small cell lung cancer cells in culture and in patient-derived xenograft models (PMID: 19276360). 19276360
BRAF wild-type melanoma predicted - sensitive Sorafenib Preclinical - Patient cell culture Actionable In a preclinical study, Nexavar (sorafenib) treatment inhibited viability of patient-derived wild-type BRAF melanoma cells in culture (PMID: 23715574). 23715574
BRAF wild-type melanoma no benefit Dabrafenib Preclinical - Patient cell culture Actionable In a preclinical study, Tafinlar (dabrafenib) treatment did not inhibit viability of patient-derived wild-type BRAF melanoma cells in culture (PMID: 23715574). 23715574
BRAF wild-type melanoma resistant GDC0879 Preclinical - Pdx & cell culture Actionable In a preclinical study, GDC0879 failed to inhibit growth of BRAF wild-type melanoma cells in cell culture, cell line xenograft models, and patient-derived xenograft models (PMID: 19276360). 19276360
BRAF wild-type melanoma predicted - sensitive Nivolumab Phase III Actionable In a Phase III trial (CheckMate-066), Opdivo (nivolumab) treatment resulted in improved overall survival and response compared to treatment with Deticene (dacarbazine) in melanoma patients with wild-type BRAF, including a 3-year overall survival (OS) rate of 51.2% vs. 21.6%, a median OS of 37.5 months vs. 11.2 months, a complete response in 19% (40/210) vs. 1.4% (3/208), and a partial response in 23.8% (50/210) vs. 13% (27/208), respectively (PMID: 30422243; NCT01721772). 30422243
Clinical Trial Phase Therapies Title Recruitment Status Covered Countries Other Countries
NCT04744831 Phase II Trastuzumab deruxtecan Trastuzumab Deruxtecan in Participants With HER2-overexpressing Advanced or Metastatic Colorectal Cancer (DESTINY-CRC02) Recruiting
NCT02318901 Phase Ib/II Ado-trastuzumab emtansine + Pembrolizumab Pembrolizumab + Trastuzumab Cetuximab + Pembrolizumab Pembrolizumab and Monoclonal Antibody Therapy in Advanced Cancer Terminated
NCT03878719 Phase I Binimetinib + Encorafenib Study of the Combination of Binimetinib and Encorafenib in Adolescent Patients With Unresectable or Metastatic BRAF V600-mutant Melanoma Recruiting
NCT02508077 Phase II Fluorouracil + Irinotecan + Leucovorin Panitumumab FOLFIRI and Panitumumab in Treating Patients With RAS and BRAF Wild-Type Metastatic Colorectal Cancer Terminated
NCT04322383 Phase II Binimetinib Binimetinib for People With Relapsed/Refractory BRAF Wild Type Hairy Cell Leukemia and Variant Recruiting
NCT01960023 Phase Ib/II Cetuximab + Neratinib Safety and Efficacy Study of Neratinib and Cetuximab to Treat Patients With Quadruple Wild-Type Metastatic Colorectal Cancer Withdrawn
NCT01802320 Phase II MK2206 Akt Inhibitor MK2206 in Treating Patients With Previously Treated Colon or Rectal Cancer That is Metastatic or Locally Advanced and Cannot Be Removed by Surgery Completed
NCT03978611 Phase I Ipilimumab + Relatlimab A Study to Assess Safety and Efficacy of Relatlimab With Ipilimumab in Participants With Advanced Melanoma Who Progressed on Anti-PD-1 Treatment Recruiting
NCT01941927 Phase II Trametinib + Uprosertib Trametinib With GSK2141795 in BRAF Wild-type Melanoma Completed
NCT04129515 Phase Ib/II Pembrolizumab NovoTTF-200A + Pembrolizumab In Melanoma Brain Metastasis Recruiting
NCT02138292 Phase I Digoxin + Trametinib A Phase 1B Clinical Trial of Trametinib Plus Digoxin in Patients With Unresectable or Metastatic BRAF Wild-type Melanoma Completed
NCT01138085 Phase I Trametinib + Uprosertib Safety, Pharmacokinetics (PK) of AKT and MEK Combination Completed
NCT03384940 Phase II Trastuzumab deruxtecan DS-8201a in Human Epidermal Growth Factor Receptor2 (HER2)-Expressing Colorectal Cancer (DESTINY-CRC01) Completed
NCT04616183 Phase Ib/II Abemaciclib + Cetuximab + LY3214996 Cetuximab + LY3214996 LY3214996 and Cetuximab Alone or in Combination With Abemaciclib for the Treatment of Unresectable or Metastatic Colorectal Cancer Recruiting
NCT02785068 Phase I Fluorouracil + Irinotecan + Leucovorin + MM-151 Evaluation of MM-151 + Nal-IRI + 5-FU + Leucovorin in RAS/RAF Wild-type Metastatic Colorectal Cancer Withdrawn
NCT03457896 Phase II Cetuximab + Neratinib Neratinib + Trastuzumab Study of Neratinib +Trastuzumab or Neratinib + Cetuximab in Patients With KRAS/NRAS/BRAF/PIK3CA Wild-Type Metastatic Colorectal Cancer by HER2 Status Recruiting
NCT03069950 Phase II Dexamethasone + Floxuridine + Fluorouracil + Irinotecan + Leucovorin + Panitumumab Study of Chemotherapy With or Without Hepatic Arterial Infusion for Patients With Unresectable Metastatic Colorectal Cancer to the Liver Withdrawn
NCT03149029 Phase II Dabrafenib + Pembrolizumab + Trametinib Pembrolizumab + Trametinib Abbreviated MAPK Targeted Therapy Plus Pembrolizumab in Melanoma Active, not recruiting
NCT04434560 Phase II Ipilimumab + Nivolumab Neoadjuvant Immunotherapy in Brain Metastases Recruiting