Capmatinib + Nivolumab

The combination of capmatinib and nivolumab represents a dual-targeted approach for treating non-small cell lung cancer (NSCLC). Capmatinib is a MET tyrosine kinase inhibitor that specifically targets MET dysregulation, while nivolumab is a PD-1 inhibitor that works as an immunotherapy agent. ## Drug Information Capmatinib (brand name Tabrecta) is a Type Ib MET tyrosine kinase inhibitor that received FDA approval in May 2020 for treating metastatic NSCLC with MET exon 14 skipping mutations[3][5]. It was first discovered in 2011 and works by selectively inhibiting the MET signaling pathway[5]. Nivolumab (brand name Opdivo) is a PD-1 inhibitor that has been approved for various cancer indications, including NSCLC, colorectal cancer, and hepatocellular carcinoma[4][6]. It functions by blocking the interaction between PD-1 and its ligands, enhancing T-cell immune responses against tumor cells. ## Clinical Development The combination of capmatinib plus nivolumab was investigated in a clinical trial (NCT02323126) for patients with pretreated EGFR wild-type NSCLC[1][5]. This study showed that the combination demonstrated clinical activity and manageable safety regardless of MET status[1]. Specifically, the trial reported a 6-month progression-free survival rate of 68.9% (95% CI 48.85–85.7) in patients with high cMet expression and 50.9% (95% CI 35.6–66.4) in those with low cMet expression[5]. However, the trial was terminated due to low accrual, although the primary endpoint data was still reported[5]. This suggests that while the combination showed promise, there were challenges in patient recruitment that affected the full completion of the study. ## Mechanism of Action The combination therapy leverages two distinct mechanisms: 1. Capmatinib targets the MET signaling pathway, which is often dysregulated in NSCLC, particularly in tumors with MET exon 14 skipping mutations[3][5]. 2. Nivolumab targets the PD-1 pathway, enhancing the immune system's ability to detect and destroy cancer cells[4][6]. The rationale for combining these agents stems from research suggesting that MET expression is involved in regulating the tumor microenvironment, including the upregulation of inhibitory molecules like PD-L1[5]. This creates a potential synergistic effect when targeting both pathways simultaneously. ## Safety Profile The combination of capmatinib plus nivolumab demonstrated manageable safety in clinical trials[1]. For individual agents, common adverse events for capmatinib include peripheral edema, nausea, fatigue, vomiting, dyspnea, and decreased appetite[3]. Nivolumab's safety profile includes immune-related adverse events that require monitoring and management[4][6]. This combination represents an ongoing area of research in the treatment landscape for NSCLC, particularly for patients who have progressed on previous therapies.

Brand names

Opdivo

Other names

capmatinib + nivolumabINC280 + Opdivo