Dr Sabari on c-MET as a Potential Biomarker of Response in EGFR Wild-Type NSCLC

"We want to look at [c-MET] as a biomarker for patients who may benefit from [telisotuzumab vedotin]. If a patient expresses high levels of MET on the surface of the cell, they can have increased binding and potentially activity of the MMAE payload. We looked at this [agent] specifically in patients with nonsquamous, EGFR wild-type, advanced NSCLC."

Joshua K. Sabari, MD, an associate professor in the Department of Medicine at New York University (NYU) Grossman School of Medicine and medical director of Thoracic Medical Oncology at NYU Langone Health’s Perlmutter Cancer Center, discussed the prevalence of and rationale behind targeting c-MET in nonsquamous, EGFR wild-type advanced NSCLC.

There has been increasing interest in exploring the role of c-MET as a biomarker in EGFR wild-type advanced NSCLC to identify patients who may benefit from targeted therapies, Sabari began. Expression of high levels of c-MET on the cell surface can lead to increased binding and potentially enhanced activity of the monomethyl auristatin E chemotherapeutic payload, Sabari explained. In the EGFR-mutant lung cancer population, MET expression is a common potential resistance mechanism, Sabari noted. However, this approach may also be relevant for patients with nonsquamous EGFR wild-type advanced NSCLC, where c-MET overexpression may predict therapeutic response, Sabari detailed.

The phase 2 LUMINOSITY trial (NCT03539536) evaluated the efficacy and safety of telisotuzumab vedotin-tllv (Emrelis) in patients with nonsquamous, EGFR wild-type advanced NSCLC with c-MET overexpression, Sabari noted. This population did not include patients with known driver mutations, focusing on patients without actionable mutations, Sabari detailed.

Data presented at the 2025 ASCO Annual Meeting showed that among patients with high c-MET protein overexpression who had previously received platinum-based chemotherapy alone (n = 81), the objective response rate (ORR) was 34.6% (95% CI, 24.3%-46.0%). Conversely, patients with high c-MET protein overexpression who had received both platinum chemotherapy and an immune checkpoint inhibitor (n = 67) achieved an ORR of 32.8% (95% CI, 21.8%-45.4%).

Notably, patients with intermediate c-MET protein overexpression demonstrated similar response outcomes regardless of prior therapy exposure, suggesting that c-MET expression level, rather than prior treatment regimen, may be the more relevant predictor of therapeutic response in this subgroup, Sabari concluded.