A phase II trial of tepotinib in patients with non-small cell lung cancer (NSCLC) harboring MET alterations: The VISION study
Authors: P. Paik, A. Cortot, E. Felip, H. Sakai, J. Mazieres, L. Horn, F. Griesinger, R. Bruns, J. Scheele, J. Straub, R. Veillon
Journal: Annals of Oncology (2019)

Background: Dysregulation of the 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% of NSCLCs, 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 of tepotinib 500 mg daily, as 1st–3rd line of treatment, in patients with histologically-confirmed, advanced (stage IIIB/IV) NSCLC (all histologies) harboring MET alterations. Patients with METex14 + (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 factor 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 of response, 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 A commenced in September 2016 and is continuing. Enrolment of patients with LBx-confirmed METamp into Cohort B commenced in September 2018; based on an interim analysis of 12 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 trial identification: NCT02864992. Editorial acknowledgement: Medical writing assistance (funded by Merck KGaA, Darmstadt, Germany) was provided by Lisa Jolly, Bioscript Science (Macclesfield, UK). Legal entity responsible for the study: Merck KGaA. Funding: Merck KGaA. Disclosure: P. Paik: Advisory board, honorarium: Celgene; IDMC: Takeda. A. Cortot: Advisory boards member: AstraZeneca, BMS, MSD, Pfizer, Novartis, Roche, Takeda, Boehringer Ingelheim; Corporate-sponsored research: Merck. E. Felip: Speaker's bureau, advisory board: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Celegene, Eli Lilly, Guardant Health, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Takeda, AbbVie, Merck. J. Mazieres: Advisory board: Roche, BMS, MSD, AstraZeneca, Pfizer, Novartis. F. Griesinger: Scientific support: ASTRA, Boehringer Ingelheim, BMS, Celgene, Lilly, MSD, Novartis, Pfizer, Roche, Takeda, Siemens; Talks, presentations, advisory boards: ASTRA, Boehringer Ingelheim, BMS, Celgene, Lilly, MSD, Novartis, Pfizer, Roche, Takeda, ARIAD, AbbVie, Siemens. R. Bruns, J. Scheele, J. Straub: Employee: Merck KGaA, Darmstadt, Germany. R. Veillon: Congress registration, advisory board: Boehringer Ingelheim, Bristol-Myers Squibb, Merck Sharp & Dohme, Roche, Pfizer, AbbVie, Merck. All other authors have declared no conflicts of interest.