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Profile Name | BRAF wild-type |
Gene Variant Detail | |
Relevant Treatment Approaches |
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 |