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| Therapy Name | Cobimetinib + Pembrolizumab + Vemurafenib |
| Synonyms | |
| Therapy Description | |
| Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
|---|---|---|---|---|
| Cobimetinib | Cotellic | GDC-0973 | MEK inhibitor (Pan) 27 MEK1 Inhibitor 28 MEK2 Inhibitor 26 | 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). |
| Pembrolizumab | Keytruda | MK-3475 | Immune Checkpoint Inhibitor 150 PD-L1/PD-1 antibody 138 | Keytruda (pembrolizumab) is an antibody against PD-1 that activates T-cell mediated anti-tumor immune response (PMID: 25977344). Keytruda (pembrolizumab) is approved in melanoma, SCLC, HNSCC, classical Hodgkin Lymphoma, PMBL, urothelial carcinoma, HCC, Merkel cell carcinoma, NMIBC, cutaneous SCC, MSI-H or dMMR or TMB high advanced solid tumors, NSCLC and CD274 (PD-L1)-positive NSCLC, esophageal SCC, cervical cancer, HNSCC, and TNBC, in combination with platnum-based chemo in NSCLC, with pemetrexed and platinum in pleural mesothelioma and non-sNSCLC with no EGFR or ALK mutations, with carboplatin and paclitaxel/nab-paclitaxel in sNSCLC, with axitinib or lenvatinib in RCC, with lenvatinib in non-MSI-H or dMMR endometrial carcinoma, with platinum and fluoropyrimidine-based chemo for esophageal or gastroesophageal carcinoma, HER2-negative gastric or GEJ adenocarcinoma, with Herceptin (trastuzumab), fluoropyrimidine- and platinum-containing chemo for CD274 (PD-L1)-positive, HER2-positive gastric or GEJ adenocarcinoma, with platinum-based chemotherapy, with or without bevacizumab, for patients with CD274 (PD-L1)-positive cervical cancer, with gemcitabine and cisplatin for biliary tract cancer, with chemoradiation for cervical cancer, with carboplatin and paclitaxel for endometrial carcinoma, with paclitaxel with or without bevacizumab for epithelial ovarian, Fallopian tube, and peritonium cancer, with Padcev for MIBC (FDA.gov). |
| Vemurafenib | Zelboraf | RO5185426|PLX4032 | RAF Inhibitor (Pan) 29 | Zelboraf (vemurafenib) inhibits BRAF V600E, wild-type BRAF, ARAF, and CRAF (PMID: 20179705), which may result in an inhibition of the MAPK signaling pathway resulting in a reduction of tumor cell proliferation (PMID: 20823850). Zelboraf (vemurafenib) is FDA approved for BRAF V600E-mutant melanoma and for BRAF V600-positive Erdheim-Chester disease (FDA.gov). |
| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| BRAF V600K | melanoma | no benefit | Cobimetinib + Pembrolizumab + Vemurafenib | Phase I | Actionable | In a Phase I trial, combination of Cotellic (cobimetinib), Zelboraf (vemurafenib), and Keytruda (pembrolizumab) resulted in unreached median progression-free survival and overall survival in patients with advanced melanoma harboring BRAF V600E or V600K mutations, however, the trial was closed due to high incidence of dose-limiting toxicity and decreased health utility at 1 year (J Clin Oncol 39, no. 15_suppl, abstract e21506; NCT02818023). | detail... |
| BRAF V600E | melanoma | no benefit | Cobimetinib + Pembrolizumab + Vemurafenib | Phase I | Actionable | In a Phase I trial, combination of Cotellic (cobimetinib), Zelboraf (vemurafenib), and Keytruda (pembrolizumab) resulted in unreached median progression-free survival and overall survival in patients with advanced melanoma harboring BRAF V600E or V600K mutations, however, the trial was closed due to high incidence of dose-limiting toxicity and decreased health utility at 1 year (J Clin Oncol 39, no. 15_suppl, abstract e21506; NCT02818023). | detail... |
| Clinical Trial | Phase | Therapies | Title | Recruitment Status | Covered Countries | Other Countries |
|---|---|---|---|---|---|---|
| NCT02818023 | Phase I | Cobimetinib + Pembrolizumab + Vemurafenib | Dose-seeking Study of Pembrolizumab Plus Vemurafenib and Cobimetinib Advanced Melanoma | Terminated | USA | 0 |