FDA Grants Accelerated Approval for Telisotuzumab Vedotin in NSCLC

In a significant advancement for lung cancer treatment, the U.S. Food and Drug Administration (FDA) granted accelerated approval to telisotuzumab vedotin (Emrelis) on May 14, 2025, for adult patients with advanced non-small cell lung cancer (NSCLC) characterized by high c-MET protein overexpression. This decision is based on promising data from the phase 2 LUMINOSITY trial (NCT03539536), which evaluated the efficacy of this novel antibody-drug conjugate in patients who had previously undergone treatment for locally advanced or metastatic nonsquamous NSCLC.

According to Dr. Jonathan Goldman, MD, who serves as the UCLA Director of Clinical Trials in Thoracic Oncology and is also the associate director of Early Drug Development, telisotuzumab vedotin represents a new therapeutic option targeting the c-MET pathway, which plays a crucial role in tumor growth and resistance to standard treatments. "The mechanism of action of telisotuzumab vedotin is distinctive in that it utilizes MET as a target to deliver a cytotoxic agent directly to tumor cells, which is particularly relevant given the prevalence of c-MET overexpression in lung cancer patients," Goldman stated in an interview following the ASCO Annual Meeting.

The LUMINOSITY trial highlighted that patients receiving telisotuzumab vedotin exhibited a 35% overall response rate (ORR), with a median duration of response (DOR) lasting 7.2 months. In particular, patients with high c-MET overexpression who had undergone prior platinum-based therapy achieved an ORR of 34.6%, as per the study's findings presented by Goldman. Furthermore, those who had previously been treated with immune checkpoint inhibitors (ICIs) demonstrated an ORR of 33.3%.

The significance of these findings cannot be overstated. With c-MET overexpression found in approximately 12% to 25% of lung cancer patients, telisotuzumab vedotin's approval opens new avenues for treatment in a patient population that has limited options after standard therapies fail. As noted by Dr. Goldman, "This drug could potentially redefine how we approach treatment for patients with c-MET overexpression, particularly in earlier lines of therapy."

The LUMINOSITY study was designed with a Simon 2-stage design and initially focused on assessing the ORR within three subgroups, ultimately expanding to include around 180 patients. Notably, adverse effects associated with telisotuzumab vedotin included manageable ocular toxicities and peripheral neuropathy, which were less severe compared to those observed with conventional chemotherapies.

As the medical community looks to the future, the confirmatory phase 3 TeliMET NSCLC-01 trial (NCT04928846) is currently underway, aimed at further validating the efficacy of telisotuzumab vedotin against standard treatments like docetaxel. Goldman expressed hope for positive outcomes from this trial, emphasizing the necessity of identifying patients most likely to benefit through appropriate MET testing.

In light of the growing incidence of lung cancer and the ongoing challenges in effectively treating advanced stages of the disease, the approval of telisotuzumab vedotin marks a crucial step forward in the landscape of oncology. Experts anticipate that this breakthrough could lead to improved patient outcomes and a shift in treatment paradigms for NSCLC, particularly for those harboring c-MET overexpression.