Therapy Detail
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| Therapy Name | Belvarafenib + Cobimetinib |
| Synonyms | |
| Therapy Description | |
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| Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
|---|---|---|---|---|
| Belvarafenib | HM95573|GDC-5573|RO7223619 | RAF Inhibitor (Pan) 28 | Belvarafenib (HM95573) selectively inhibits RAF dimer formation, leading to inhibition of ARAF, BRAF, and CRAF activity, and potentially resulting in tumor growth inhibition (PMID: 33953400). | |
| Cobimetinib | Cotellic | GDC-0973 | MEK inhibitor (Pan) 26 MEK1 Inhibitor 26 MEK2 Inhibitor 24 | Cotellic (cobimetinib) is an allosteric inhibitor of MEK1/2, resulting in inhibition of extracellular signal-related kinase 2 (ERK2) phosphorylation and activation and decreased tumor cell proliferation (PMID: 22084396, PMID: 27956260). Cotellic (cobimetinib) is FDA approved for use in combination with Zelboraf (vemurafenib) in melanoma patients harboring BRAF V600E or V600K (FDA.gov). |
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| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| BRAF V600X | Advanced Solid Tumor | predicted - sensitive | Belvarafenib + Cobimetinib | Phase I | Actionable | In a Phase Ib trial, combination treatment with Belvarafenib (HM95573) and Cotellic (cobimetinib) was well-tolerated and demonstrated safety, and led to a confirmed partial response in 33.3% (3/9) solid tumor patients harboring BRAF V600 mutations (Annals of Oncology 32 (2021): S595; NCT03284502). | detail... |
| BRAF V600D | melanoma | sensitive | Belvarafenib + Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, the addition of Cotellic (cobimetinib) to treatment with Belvarafenib (HM95573) in a melanoma cell line harboring BRAF V600D resulted in greater inhibition of cell proliferation in culture compared to single agent alone (PMID: 33953400). | 33953400 |
| BRAF fusion | Advanced Solid Tumor | predicted - sensitive | Belvarafenib + Cobimetinib | Phase I | Actionable | In a Phase I trial (HM-RAFI-103), Belvarafenib (HM95573) and Cotellic (cobimetinib) combination therapy demonstrated preliminary activity in patients with advanced solid tumors harboring BRAF fusions, resulting in an objective response rate of 60% (9/15, all partial responses), a disease control rate of 93.3% (14/15), with a median progression-free survival of 13.7 months, and a median duration of response of 12 months (Ann Oncol 34 (2023): S465; NCT03284502). | detail... |
| NRAS mutant | melanoma | predicted - sensitive | Belvarafenib + Cobimetinib | Phase I | Actionable | In a Phase I trial, Belvarafenib (HM95573) and Cotellic (cobimetinib) combination therapy was tolerable, and resulted in a response rate of 38% (5/13, 5 partial response) in patients with melanoma harboring NRAS mutations, with a median progression-free survival of 7.3 months (J Clin Oncol 39, no. 15_suppl (May 20, 2021) 3007-3007; NCT03284502). | detail... |
| NRAS Q61L | melanoma | sensitive | Belvarafenib + Cobimetinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the addition of Cotellic (cobimetinib) to treatment with Belvarafenib (HM95573) in melanoma cell lines harboring NRAS Q61L resulted in greater inhibition of cell proliferation in culture compared to single agent alone, and led to decreased tumor volume, with increased efficacy and response durability in a cell line xenograft model (PMID: 33953400). | 33953400 |
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| Clinical Trial | Phase | Therapies | Title | Recruitment Status | Covered Countries | Other Countries |
|---|---|---|---|---|---|---|
| NCT04835805 | Phase I | Belvarafenib + Cobimetinib + Nivolumab Belvarafenib + Cobimetinib Belvarafenib | A Study to Evaluate the Safety and Activity of Belvarafenib as a Single Agent and in Combination With Either Cobimetinib or Cobimetinib Plus Nivolumab in Patients With NRAS-mutant Advanced Melanoma. | Active, not recruiting | USA | NOR | DEU | CAN | AUS | 1 |
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