A Phase 1b Study of Telisotuzumab Vedotin in Combination With Nivolumab in Patients With NSCLC
Year: 2021
Type: article
Study design: Clinical Trial
Abstract: INTRODUCTION: Telisotuzumab vedotin (Teliso-V) is an anti-c-Met-directed antibody-drug conjugate that has exhibited antitumor activity as monotherapy in NSCLC. Its potential activity combined with programmed cell death protein-1 inhibitors has not been previously evaluated. METHODS: In a phase 1b study (NCT02099058), adult patients (≥18 y) with advanced NSCLC received combination therapy with Teliso-V (1.6, 1.9, or 2.2 mg/kg, every 2 wk) plus nivolumab (3 mg/kg, 240 mg, or per locally approved label). The primary objective was to assess safety and tolerability; secondary objectives included the evaluation of antitumor activity. RESULTS: As of January 2020, a total of 37 patients received treatment with Teliso-V (safety population) in combination with nivolumab; 27 patients (efficacy population) were c-Met immunohistochemistry-positive. Programmed death-ligand 1 (PD-L1) status was evaluated in the efficacy population (PD-L1-positive [PD-L1+]: n = 15; PD-L1-negative [PD-L1-]: n = 9; PD-L1-unknown: n = 3). The median age was 67 years and 74% (20 of 27) of patients were naive to immune checkpoint inhibitors. The most common any-grade treatment-related adverse events were fatigue (27%) and peripheral sensory neuropathy (19%). The pharmacokinetic profile of Teliso-V plus nivolumab was similar to Teliso-V monotherapy. The objective response rate was 7.4%, with two patients (PD-L1+, c-Met immunohistochemistry H-score 190, n = 1; PD-L1-, c-Met H-score 290, n = 1) having a confirmed partial response. Overall median progression-free survival was 7.2 months (PD-L1+: 7.2 mo; PD-L1-: 4.5 mo; PD-L1-unknown: not reached). CONCLUSIONS: Combination therapy with Teliso-V plus nivolumab was well tolerated in patients with c-Met+ NSCLC with limited antitumor activity.
Authors: D. Ross Camidge, Fabrice Barlesi, Jonathan W. Goldman, Daniel Morgensztern, Rebecca Heist, Everett Vokes, Eric Angevin, David S. Hong, Igor I. Rybkin, Minal Barve, Todd M. Bauer, Angelo Delmonte, Martin Dunbar, Monica Motwani, Apurvasena Parikh, Elysa Noon, Jun Wu, Vincent Blot, Karen Kelly
Institutions: University of Colorado Cancer Center, Centre National de la Recherche Scientifique, Inserm, Aix-Marseille Université, Institut Gustave Roussy, Assistance Publique Hôpitaux de Marseille, Centre de Recherche en Cancérologie de Marseille, University of California, Los Angeles, Washington University in St. Louis, Massachusetts General Hospital, University of Chicago, Fondation Gustave Roussy, The University of Texas MD Anderson Cancer Center, Henry Ford Health, Mary Crowley Cancer Research Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, AbbVie (United States), UC Davis Comprehensive Cancer Center
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,000
Funders: Boehringer Ingelheim, Amgen, Bristol-Myers Squibb, Eli Lilly and Company, Pfizer, Astellas Pharma US, AstraZeneca, GlaxoSmithKline, Merck, Novartis, Roche, Sanofi, Medtronic, Gilead Sciences, American Society of Clinical Oncology, Celgene, AbbVie, Takeda Pharmaceuticals U.S.A., Exelixis, Les Laboratories Pierre Fabre, Bayer Fund, Agios Pharmaceuticals, Calithera Biosciences, Aileron Therapeutics, Apollomics, G1 Therapeutics, Eisai, MedImmune, Aptitude Health, Genentech, EMD Serono, Ignyta, Janssen Pharmaceuticals, Daiichi Sankyo Europe
OpenAlex ID: W4200028613