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|Therapy Name||Atezolizumab + Cobimetinib + Vemurafenib|
|Drug Name||Trade Name||Synonyms||Drug Classes||Drug Description|
|Atezolizumab||Tecentriq||RG7446|MPDL3280A||Immune Checkpoint Inhibitor 98 PD-L1/PD-1 antibody 69||Tecentriq (atezolizumab) is a monoclonal antibody against PD-L1 (CD274), preventing activation of its receptor, potentially enhancing T-cell-mediated immune response to neoplasms and inhibiting T-cell inactivation (PMID: 29449897). Tecentriq (atezolizumab) is FDA approved for use in PD-L1 positive advanced or metastatic urothelial carcinoma not eligible for cisplatin-containing chemotherapy, in advanced or metastatic urothelial carcinoma not eligible for chemotherapy or progressed on platinum-based chemotherapy, in metastatic non-small cell lung cancer (NSCLC) progressed on platinum-containing therapy, as first-line therapy in metastatic NSCLC with high PD-L1 expression (TC>=50% or IC>=10%) and without EGFR or ALK alterations, in combination with bevacizumab, paclitaxel, and carboplatin as first-line therapy for non-squamous NSCLC with no EGFR or ALK aberrations, in combination with paclitaxel protein-bound and carboplatin in metastatic non-squamous NSCLC with no EGFR or ALK aberrations, in combination with paclitaxel protein-bound in advanced or metastatic triple-negative breast cancer expressing PD-L1, in combination with carboplatin and etoposide in extensive-stage small cell lung cancer, in combination with bevacizumab in hepatocellular carcinoma without prior systemic therapy, and in combination with cobimetinib and vemurafenib in BRAF V600-mutated melanoma (FDA.gov).|
|Cobimetinib||Cotellic||GDC-0973||MEK inhibitor (Pan) 22 MEK1 Inhibitor 20 MEK2 Inhibitor 18||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).|
|Vemurafenib||Zelboraf||RO5185426|PLX4032||RAF Inhibitor (Pan) 17||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 V600X||melanoma||sensitive||Atezolizumab + Cobimetinib + Vemurafenib||Phase Ib/II||Actionable||In a Phase Ib trial, the combination therapy of Tecentriq (atezolizumab), Zelboraf (vemurafenib), and Cotellic (cobimetinib) in patients with metastatic melanoma harboring a BRAF V600 mutation resulted in a best objective response rate of 71.8% (28/39), with a complete response in 20.5% (8/39), a median progression-free survival of 12.9 months, a median overall survival not yet reached, and median duration of confirmed response of 17.4 months (PMID: 31171876; NCT01656642).||detail... 31171876|
|BRAF V600X||melanoma||sensitive||Atezolizumab + Cobimetinib + Vemurafenib||FDA approved||Actionable||In a Phase III trial (IMspire150) that supported FDA approval, addition of Tecentriq (atezolizumab) to Zelboraf (vemurafenib) and Cotellic (cobimetinib) combination therapy significantly improved progression-free survival (15.1 vs 10.6 months, HR=0.78, p=0.025) compared to control in patients with advanced or metastatic melanoma harboring BRAF V600 mutations (PMID: 32534646; NCT02908672).||32534646 detail...|
|BRAF V600X||skin melanoma||sensitive||Atezolizumab + Cobimetinib + Vemurafenib||Guideline||Actionable||Tecentriq (atezolizumab), Zelboraf (vemurafenib), and Cotellic (cobimetinib) combination therapy is included in guidelines as a preferred first-line therapy for patients with metastatic or unresectable cutaneous melanoma harboring a BRAF V600 activating mutation (NCCN.org).||detail...|
|Clinical Trial||Phase||Therapies||Title||Recruitment Status||Covered Countries||Other Countries|
|NCT03178552||Phase II||Entrectinib Carboplatin + Cisplatin + Gemcitabine Atezolizumab Carboplatin + Cisplatin + Pemetrexed Disodium Atezolizumab + Cobimetinib + Vemurafenib Alectinib||A Study to Evaluate Efficacy and Safety of Multiple Targeted Therapies as Treatments for Participants With Non-Small Cell Lung Cancer (NSCLC) (B-FAST)||Recruiting||USA | CAN||26|
|NCT01656642||Phase I||Atezolizumab + Cobimetinib + Vemurafenib Atezolizumab + Vemurafenib||A Phase 1b Study of Atezolizumab in Combination With Vemurafenib or Vemurafenib Plus Cobimetinib in Participants With BRAFV600-Mutation Positive Metastatic Melanoma||Completed||USA||0|
|NCT02908672||Phase III||Cobimetinib + Vemurafenib Atezolizumab + Cobimetinib + Vemurafenib||A Study of Atezolizumab Plus Cobimetinib and Vemurafenib Versus Placebo Plus Cobimetinib and Vemurafenib in Previously Untreated BRAFv600 Mutation-Positive Patients With Metastatic or Unresectable Locally Advanced Melanoma||Active, not recruiting||USA | CAN||18|
|NCT03181100||Phase II||Atezolizumab + Cobimetinib Atezolizumab + Bevacizumab Atezolizumab + Nab-paclitaxel Atezolizumab + Cobimetinib + Vemurafenib Atezolizumab + Paclitaxel||Atezolizumab With Chemotherapy in Treating Patients With Anaplastic or Poorly Differentiated Thyroid Cancer||Recruiting||USA||0|
|NCT03554083||Phase I||Atezolizumab + Cobimetinib Atezolizumab + Cobimetinib + Vemurafenib||Vemurafenib, Cobimetinib, and Atezolizumab in Treating Participants With High-Risk Stage III Melanoma||Recruiting||USA||0|