Dr Girard on Findings From the LUMINOSITY Trial in c-Met–Overexpressing NSCLC

Nicolas Girard, MD, professor, respiratory medicine, Versailles Saint Quentin University; head, Curie-Montsouris Thorax Institute, chair, Medical Oncology Department, Institut Curie, discusses both the design and the main efficacy findings of the phase 2 LUMINOSITY trial (NCT03539536) in patients with c-Met protein–overexpressing, EGFR wild-type, nonsquamous non–small cell lung cancer (NSCLC).

Notably, this clinical investigation evaluated telisotuzumab vedotin (Teliso-V) in this patient population; data were shared at the 2024 ESMO Congress. In later lines of treatment, such as the second- and third-line settings following prior exposure to chemotherapy and immunotherapy, the standard of care for these patients remains docetaxel, Girard begins. However, this chemotherapy offers limited efficacy, with response rates ranging from approximately10% to 20% and a median progression-free survival of approximately 3 to 5 months, he says. Given the limited effectiveness of docetaxel following progression on prior chemotherapy and immunotherapy, new treatment options are being explored, according to Girard. One such option is Teliso-V, an antibody-drug conjugate that targets c-MET, which is a protein involved in cancer growth, Girard explains.

In the LUMINOSITY study, Teliso-V was administered every 2 weeks to patients with NSCLC selected based on c-MET expression, as determined by immunohistochemistry, he continues. Tumors were classified as c-MET overexpressing (≥ 25% of tumor cell expression with immunohistochemistry [IHC] 3+ staining), c-MET intermediate (≥ 25% to < 50% tumor cell expression with IHC 3+), or c-MET high (≥ 50% tumor cell expression with IHC 3+), Girard emphasizes. The study population primarily included patients with nonsquamous carcinomas and EGFR wild-type tumors, excluding those with EGFR oncogenic addiction, he notes.

The results of the single-arm LUMINOSITY trial demonstrated an overall response rate (ORR) of 28.6% in patients with c-Met overexpression, with a higher ORR of 34.6% in the c-MET–high subgroup, surpassing the efficacy of standard docetaxel therapy, Girard expands. The toxicity profile of Teliso-V included both chemotherapy-related adverse effects (AEs), such as hematologic toxicity, and antibody-related AEs, including interstitial lung disease, keratitis, and peripheral neuropathy, he reports. These results indicate that Teliso-V could offer a more effective treatment alternative to docetaxel in this patient population, Girard concludes.