Tony S. Mok, MD, spoke about future research efforts focused on capmatinib plus pembrolizumab in patients with previously untreated MET-unselected, PD-L1–positive non–small cell lung cancer.
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, at the 2022 American Society of Clinical Oncology Annual Meeting about future analyses of pembrolizumab (Keytruda) plus capmatinib (Tabrecta) after results from a phase 2 trial (NCT04139317) in patients with MET-unselected, PD-L1–positive previously untreated non–small cell lung cancer failed to show an advantage of the combination.
Results from this trial indicated that capmatinib did not improve antitumor activity, but Mok notes that negative trials are important in the lung cancer space as it allows clinicians to learn from the results.
We have made a very good hypothesis, but I think there’s 1 point that we neglected to look into in great detail. When we looked at the dose of capmatinib, we were using the dose that is supposed to inhibit the cancer cell MET expression. This is mostly [found] in the patient with either MET amplification or MET 14 skipping [mutation]. That’s what the drug was designed for. The question is that we have not actually investigated is the dose required to moderate the T cell. We had a dose issue where it may or may not be feasible in the future to use the same drug combination. The concept is not exactly gone yet. We may have to go back to the drawing board to determine how best to moderate the T cell with the MET inhibitor in the future.
This is a negative study, but we can always learn from the negative studies. First, the concept itself is a good one. That’s why we get engaged with it. However, [regarding] the dosing part, we did not address it. Before we engage in it, we automatically [choose] the standard dose which is easier in that way. Again, we have to learn from the fact that dosing potentially may affect the outcome.
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