Who May Benefit From Telizotuzumab Vedotin in NSCLC? LUMINOSITY Trial Sheds Light

By: Celeste L. Dixon
Posted: Monday, August 12, 2024

The phase II LUMINOSITY trial researchers used a two-stage design to meet their goal of identifying a highly suitable non–small cell lung cancer (NSCLC) population to be treated with telisotuzumab vedotin, an antibody-drug conjugate directed against the c-Met protein with a monomethyl auristatin E cytotoxic payload. The agent was most associated with durable responses in c-Met protein–overexpressing (especially high-expressing), nonsquamous, EGFR–wild-type NSCLC. D. Ross Camidge, MD, PhD, of the University of Colorado Cancer Center, Aurora, and colleagues described their work in the Journal of Clinical Oncology.

The study’s primary endpoint was overall response rate. By stage 2, all participating patients (n = 172) had locally advanced or metastatic disease with the characteristics noted above, as well as two or fewer prior lines of therapy that included one or fewer lines of systemic chemotherapy. The definition of c-Met protein overexpression was 25% or more tumor cells with staining at 3+ intensity (high expression, 50% or higher; intermediate, 25%–49%).

The overall response rate was 28.6%. For disease with c-Met high and c-Met intermediate overexpression, respectively, the rates had notable variation: 34.6% and 22.9%, respectively.

In contrast, the median duration of response, progression-free survival, and overall survival (8.3, 14.5, and 5.7 months, respectively) were comparable among patients with c-Met high and c-Met intermediate overexpression. This finding is “consistent with the reduction in tumor burden observed in most patients,” the authors wrote. Adverse events were reported to be generally manageable.

These results inform an ongoing phase III trial of telisotuzumab vedotin vs docetaxel in this patient population, noted Dr. Camidge and co-investigators. In addition, “Preclinical data suggest an interaction between the mechanisms of action for telisotuzumab vedotin and osimertinib [that] may improve response to the combination,” they said.

Disclosure: For full disclosures of the study authors, visit ascopubs.org.

Journal of Clinical Oncology

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