1501TiP - A phase III global study of telisotuzumab vedotin versus docetaxel in previously treated patients with c-Met overexpressing, EGFR wildtype, locally advanced/metastatic nonsquamous NSCLC (TeliMET NSCLC-01)

Background

Non-small cell lung cancer (NSCLC) encompasses over two-thirds of lung cancer diagnoses, most presenting as advanced disease. c-Met (MET protein) is overexpressed in NSCLC. In this study, we investigate telisotuzumab vedotin (Teliso-V), a first-in-class antibody-drug conjugate composed of a c-Met–targeting antibody (telisotuzumab) and a microtubule polymerization inhibitor (cytotoxin monomethyl auristatin E). Interim efficacy analysis of the phase 2 LUMINOSITY study (NCT03539536) of Teliso-V monotherapy showed an objective response rate (ORR) of 37% (95% CI: 24–51) in previously treated patients (pts) with c-Met overexpressing epidermal growth factor receptor (EGFR) wildtype (WT) nonsquamous NSCLC and 52% (95% CI: 31–73) in the high c-Met overexpressing group.

Trial design

This randomized, open-label, global phase 3 study (NCT04928846) evaluates the efficacy, safety, pharmacokinetics, and pharmacodynamics of Teliso-V monotherapy compared with docetaxel in pts with locally advanced/metastatic c-Met overexpressing EGFR WT nonsquamous NSCLC who have progressed on prior therapy. Enrollment began in May 2022. To be eligible across global sites, pts must be ≥18 years old with c-Met overexpressing (ie, ≥25% tumor cells at 3+ intensity by IHC assay [anti-MET clone SP44; Roche Tissue Diagnostics]) locally advanced/metastatic EGFR WT NSCLC, with ECOG score ≤1. Pts must have progressed on at least one prior line of therapy, which can include no more than one line of prior chemotherapy, and must be naïve to c-Met–targeted antibodies and docetaxel. Target enrollment is 698 pts. Pts will be randomized 1:1 to Teliso-V (1.9 mg/kg every 2 weeks) and docetaxel (control, 75 mg/m² every 3 weeks). Treatment continues until disease progression or discontinuation criteria are met. Co-primary endpoints are progression-free survival by independent central review and overall survival. Secondary endpoints include ORR, duration of response, and patient-reported outcomes. Safety, adverse events (AEs), drug discontinuation or dosing modification due to AEs, and tolerability will be assessed.

Clinical trial identification

NCT04928846.

Editorial acknowledgement

Medical writing support was provided by Ana Lopez, PhD, of Fishawack Facilitate Ltd, and funded by AbbVie.

Legal entity responsible for the study

AbbVie.

Funding

AbbVie.

Disclosure

A. Lugini: Financial Interests, Personal and Institutional, Advisory Role: Roche, MSD, Boehringer Ingelheim, AstraZeneca, BMS, Sanofi-Regeneron. J.W. Goldman: Financial Interests, Personal and Institutional, Research Grant: AbbVie, AstraZeneca, Bristol Myers Squibb, Eli Lilly and Company, Genentech, Merck, Pfizer; Financial Interests, Personal and Institutional, Advisory Role: AbbVie, AstraZeneca, Bristol Myers Squibb, Genentech, Pfizer. J. Tanizaki: Financial Interests, Personal and Institutional, Invited Speaker: AstraZeneca, Boehringer Ingelheim , Bristol Myers Squibb, Chugai Pharmaceutical, Daiichi Sankyo, Eli Lilly, Janssen Pharmaceutical, MSD, Nihon Medi-Physics, Nippon Kayaku, Taiho Pharmaceutical, Ono Pharmaceutical, Pfizer; Financial Interests, Personal and Institutional, Advisory Role: Boehringer Ingelheim. H. Akamatsu: Financial Interests, Personal and Institutional, Other, Lecturer: MSD, Eli Lily, Amgen Inc, Chugai Pharmaceutical, Ono Pharmaceutical, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Novartis Pharma, Taiho Pharmaceutical, Pfizer, Nippon Kayaku, Daiichi Sankyo, Janssen Pharma; Financial Interests, Personal and Institutional, Research Grant: MSD, Eli Lilly, Amgen Inc. S. Xia, C. Ratajczak, M. Li, E. Bolotin,J. Seraj: Financial Interests, Personal and Institutional, Full or part-time Employment, May hold stock or options: AbbVie. S. Lu: Financial Interests, Personal and Institutional, Research Grant: AstraZeneca, Hutchison, Bristol Myers Squibb, Heng Rui, Roche; Financial Interests, Personal and Institutional, Invited Speaker: AstraZeneca, Roche, Hansoh; Financial Interests, Personal and Institutional, Advisory Role: AstraZeneca, Boehringer Ingelheim, Hutchison, MediPharma, Simcere, ZaiLab, GenomiCare, Roche.