Phase 1 Study of Telisotuzumab Vedotin in Patients with c-Met–Mutated Advanced NSCLC

Telisotuzumab vedotin (teliso-V), an anti–c-Met antibody conjugated with a tubulin inhibitor payload, is active in selected patients with advanced c-Met–positive non–small-cell lung cancer (NSCLC).

Telisotuzumab vedotin (teliso-V) is an anti–c-Met antibody conjugated with a tubulin inhibitor cytotoxic agent. The aim of this phase 2 trial was to explore safety and efficacy of teliso-V in cohorts of patients with c-Met–positive advanced non–small-cell lung cancer (NSCLC) based on their histopathology and EGFR mutation status, as well as patient subgroups based on c-Met expression (stage 1), followed by expansion into an appropriately selected population for further evaluation of safety and efficacy (stage 2).1

Patients enrolled in this study of teliso-V had an Eastern Cooperative Oncology Group performance status score of 0 or 1 and received 1 or 2 prior lines of therapy for NSCLC, including cytotoxic chemotherapy, immunotherapy, and targeted therapy. Their c-Met status was determined centrally by immunohistochemistry (IHC, SP44 antibody). Membrane staining ≥25% 3+ or ≥75% 1+ was considered positive for nonsquamous and squamous NSCLC, respectively. The dose of teliso-V was 1.9 mg/kg every 2 weeks. The study’s primary end point was objective response rate (ORR) per central review in patients with at least 12 weeks of follow-up. Secondary end points were duration of response, disease control rate, progression-free survival, and overall survival.1

In the nonsquamous EGFR wild-type (WT) cohort, the ORR associated with teliso-V was 35.1%. In the c-Met high group, ORR was 53.8%, while in the c-Met intermediate group, ORR was 25.0%. The ORR was deemed “modest” in the squamous and EGFR-mutated cohorts.1

Grade ≥3 adverse events (AEs) occurred in 44% of patients receiving teliso-V. The most common events (≥2%) were malignant neoplasm progression (6.2%), pneumonia (5.3%), hyponatremia (4.4%), anemia (2.7%), dyspnea (2.7%), fatigue (2.7%), increased GGT (2.7%), peripheral sensory neuropathy (2.7%), and pneumonitis (2.7%). Grade 5 AEs that investigators considered possibly related to teliso-V were sudden death, dyspnea, and pneumonitis (1 event each).1

Researchers summarized by sharing that the ORR in nonsquamous EGFR WT NSCLC was encouraging enough to move this patient cohort to stage 2 of the teliso-V trial. In this cohort, ORR was highest in the c-Met high group, although also clinically meaningful in the c-Met intermediate group. Enrollment in the squamous NSCLC cohort was stopped, while enrollment into the EGFR-mutated cohort continues until the next interim analysis.1

1. Camidge DR, Moiseenko F, Cicin I, et al. Telisotuzumab vedotin (teliso-v) monotherapy in patients with previously treated c-Met+ advanced non-small cell lung cancer. Presented at: American Association of Cancer Research Annual Meeting 2021; April 10-15, 2021. Abstract CT179.