Dr Goldman on the Efficacy of Telisotuzumab Vedotin in Advanced NSCLC With c-MET Overexpression

“The primary end point of LUMINOSITY was the objective response rate in the c-MET–high group. It was 35%, so it was meaningfully superior to 2 other FDA-approved agents in the second-line setting.”

Jonathan W. Goldman, MD, a professor of medicine in the Hematology/Oncology Division, director of Clinical Trials in Thoracic Oncology, and associate director of Early Drug Development at UCLA Medical Center, discusses the efficacy of telisotuzumab vedotin-tllv (Emrelis) in the treatment of patients with nonsquamous, EGFR wild-type, advanced non–small cell lung cancer (NSCLC) with c-MET overexpression, based on prior therapy, in the phase 2 LUMINOSITY trial (NCT03539536).

In May 2025, the FDA granted accelerated approval to telisotuzumab vedotin for the treatment of adult patients with locally advanced or metastatic, nonsquamous NSCLC who harbor high c-MET protein overexpression and have previously received systemic therapy. The regulatory decision was based on data from the LUMINOSITY trial; findings supporting the approval revealed that patients with high c-MET protein overexpression treated with the agent (n = 84) experienced an overall response rate (ORR) of 35% (95% CI, 24%-46%), of which all responses were partial responses. Additionally, the median duration of response (DOR) was 7.2 months (95% CI, 4.2-12), with 6- and 12-month DOR rates of 59% and 21%, respectively.

The study’s primary end point was ORR, Goldman began. Among patients with high c-MET protein expression, the ORR was meaningfully superior vs historical data for other agents that have been FDA-approved in the second-line setting, he noted.

In an another analysis of data from LUMINOSITY presented at the 2025 ASCO Annual Meeting, findings patients with high c-MET protein overexpression previously treated with platinum chemotherapy alone (n = 81) experienced an ORR of 34.6%, whereas those previously treated with platinum and an immune checkpoint inhibitor (n = 67) achieved an ORR of 32.8%. Patients with intermediate c-MET protein overexpression had similar response outcomes irrespective of prior therapy.

Regarding safety, the integration of antibody-drug conjugates with MMAE payloads into clinical practice has led to novel toxicities associated with this class of agents, Goldman said. Ocular toxicities represent 1 of these adverse effects (AEs), he continued. However, instances of these AEs have been low and generally mild with telisotuzumab vedotin, he noted. Peripheral neuropathy is another AE of concern, but Goldman explained that unlike taxane neuropathy, he has found peripheral neuropathy to be reversible with telisotuzumab vedotin. The emergence of neuropathy can also stem from a longer-term duration on treatment, Goldman added.

The open-label, single-arm study included patients 18 years of age or older with locally advanced or metastatic nonsquamous and EGFR wild-type NSCLC, including high c-MET overexpression per immunohistochemistry testing. Those on the study were required to have experienced disease progression after or intolerance to systemic cytotoxic therapy, previously received an immune checkpoint inhibitor with or without chemotherapy, and targeted anticancer therapies if indicated. Specifically, no more than 2 prior lines of systemic therapy were allowed in the locally advanced or metastatic setting, which included 1 line of chemotherapy. Multiple prior lines of TKIs were allowed as 1 line of treatment. Of note, patients were also required to have an ECOG performance status of 0 or 1.