A phase II trial of tepotinib in patients with non-small cell lung cancer (NSCLC) harboring MET alterations: The VISION study

Abstract

Background: Dysregulation ofthe MET pathway is common in human carcinomas and leads to dependency on MET signalling, representing a potential therapeutic target in NSCLC.MET alterations including MET-exon 14 skipping mutations (METex14) and MET amplification (METamp) are known oncogenic drivers, and occur in 3–4% and 0.4–1.5% ofNSCLCs, respectively. Tepotinib, a potent selective, small molecule MET inhibitor, has shown promise in preclinical and phase 1 trials. Trial design: VISION (NCT02864992), a single-arm, open-label, multicentre Phase 2 trial, will assess the antitumour activity and tolerability oftepotinib 500 mg daily, as 1st–3rd line oftreatment, in patients with histologically-confirmed, advanced (stage IIIB/IV) NSCLC (all histologies) harboring MET alterations. Patients with METex14þ(determined by tumor biopsy [TBx] and/or plasma ‘liquid’ biopsy [LBx]; Cohort A) or METamp (determined by LBx; Cohort B) NSCLC are included. Prior treatment with checkpoint inhibitors is permitted. Patients with epidermal growth fac- tor receptor-activating mutations, anaplastic lymphoma kinase rearrangements, or with brain metastasis as the only measurable lesion are excluded. The primary endpoint is objective response rate (ORR) by independent review committee via Response Evaluation Criteria in Solid Tumors v1.1. Secondary objectives include investigator- assessed ORR, duration ofresponse, disease control, progression free survival, overall survival, tolerability, and safety. Adverse events (AEs) will be monitored throughout the study and for 30 days (90 days for serious AEs) after treatment and graded per National Cancer Institute Common Terminology Criteria for Adverse Events v4.0. Enrolment into Cohort Acommenced in September 2016 and is continuing. Enrolment ofpatients with LBx-confirmed METamp into Cohort B commenced in September 2018; based on an interim analysis of12 patients, recruitment may continue to enrol ?60 patients. This abstract was previously presented at ESMO Asia 2018, FPN 546TiP, Paik et al. Reused with permission. Clinical