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

Reference
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.