Tony S. Mok, MD, Reviews Capmatinib Plus Pembrolizumab in Previously Untreated NSCLC

Video

Tony S. Mok, MD, spoke about the use of capmatinib plus pembrolizumab in patients with previously untreated non–small cell lung cancer who were MET unselected and had PD-L1 expression of 50% or more.

At the 2022 American Society of Clinical Oncology Annual Meeting, CancerNetwork® spoke with Tony S. Mok, MD, Li Shu Fan Medical Foundation Named Professor of Clinical Oncology and chair of Clinical Oncology at the Chinese University of Hong Kong, about a recent phase 2 trial (NCT04139317) which investigated pembrolizumab (Keytruda) plus capmatinib (Tabrecta) in patients with MET unselected, PD-L1–positive previously untreated non–small cell lung cancer.

Of evaluable patients treated, the objective response rate was 15.7% (95% CI, 7.0%-28.6%) in the combination arm and 28.0% (95% CI, 12.1%-49.4%) with pembrolizumab alone. Additionally, the disease control rates were 56.9% vs 56.0% in the combination and pembrolizumab alone arms, respectively.

Transcript:

We know that pembrolizumab is an anti–PD-1 [agent] that had been a current standard [of treatment] for patients who have over 50% expression of PD-L1. On the other hand, capmatinib is a rather potent MET inhibitor. The MET inhibitor can inhibit MET in the cancer cell, but at the same time it may also affect MET in the T cell. There are preclinical data suggesting that the inference in the T cell can potentially affect the T cell ability to kill the cancer cell. Based on this so-called background hypothesis, we combined a potent MET inhibitor with pembrolizumab for patients who are over 50% of PD-L1 expression.

This is a randomized phase 2 study, where the objective is to see whether there is a signal that may improve efficacy. Unfortunately, in the sample that we collected, there is a no signal of any improvement in the progression-free survival. On the other hand, the patient who received capmatinib in combination [with pembrolizumab] had additional toxicity. They are mostly MET related, like edema and hepatic toxicity. Overall, there is added toxicity but not much signal that it may improve efficacy. That’s why the study was terminated slightly early.

Reference

Mok T, Cortinovis D, Majem M, et al. Efficacy and safety of capmatinib plus pembrolizumab in treatment (tx)-naïve patients with advanced non–small cell lung cancer (NSCLC) with high tumor PD-L1 expression: Results of a randomized, open-label, multicenter, phase 2 study. J Clin Oncol. 2022;40(suppl 16):9118. doi:10.1200/JCO.2022.40.16_suppl.9118

Related Videos
Common adverse effects following treatment with lenvatinib plus pembrolizumab in the phase 3 CLEAR study include diarrhea, hypertension, and fatigue, according to Thomas E. Hutson, DO, PharmD, FACP.
Lenvatinib in combination with pembrolizumab appears to raise no new safety signals in patients with advanced clear cell renal cell carcinoma after 4 years of follow-up in the phase 3 CLEAR study.
According to Thomas E. Hutson, DO, PharmD, FACP, 4-year follow-up data from the phase 3 CLEAR study confirm the maintained benefits of lenvatinib plus pembrolizumab in patients with advanced renal cell carcinoma.
Findings from the phase 3 MIRASOL trial support mirvetuximab soravtansine as a standard treatment option for platinum-resistant ovarian cancer, according to Ritu Salani, MD.
Rana R. McKay, MD discusses presentations of interest that were presented at the 2023 Kidney Cancer Research Summit, including a discussion on how PET imaging may identify which patients with renal cell carcinoma may respond to immunotherapy.
A better understanding of tumor biology may be necessary for identifying novel non-immunotherapy–based therapeutic strategies for patients with renal cell carcinoma, according to Rana R. McKay, MD.
Probiotics and other agents targeting fatty acid oxidation are also under evaluation as treatment options for patients with renal cell carcinoma, according to Rana R. McKay, MD.
Other angiogenic agents are also under investigation in renal cell carcinoma, according to Rana McKay, MD, who indicates it will be interesting to see how they compare with belzutifan.
Expert on NSCLC