Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2022

Tepotinib in patients with MET exon 14 (METex14) skipping NSCLC: Analysis of all patients from VISION Cohorts A and C (#279)

Malinda Itchins 1 , Michael Thomas 2 , Marina Garassino 3 , Enriqueta Felip 4 , Hiroshi Sakai 5 , Xiuning Le 6 , Remi Veillon 7 , Egbert Smit 8 , Julien Mazieres 9 , Alexis Cortot 10 , Jo Raskin 11 , Santiago Viteri 12 , James Yang 13 , Myung-Ju Ahn 14 , Yi-Long Wu 15 , Rui Ma 16 , Jun Zhao 17 , Aurora O'Brate 18 , Karin Berghoff 19 , Rolf Bruns 20 , Gordon Otto 21 , Paul Paik 22
  1. North Shore Private Hospital, St Leonards, NSW, Australia
  2. Thoraxklinik, University Heidelberg and Translational Lung Research Center Heidelberg (TLRC-H), The German Center for Lung Research (DZL), Heidelberg, Germany
  3. Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, Department of Medicine, Section of Hematology/Oncology, Knapp Center for Biomedical Discovery, The University of Chicago, IL, USA
  4. Department of Oncology, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain
  5. Department of Thoracic Oncology, Saitama Cancer Center, Saitama, Japan
  6. Department of Thoracic Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
  7. CHU Bordeaux, service des maladies respiratoires, Bordeaux, France
  8. Department of Thoracic Oncology, Netherlands Cancer Institute , Amsterdam, The Netherlands
  9. CHU de Toulouse, Institut Universitaire du Cancer, Toulouse, France
  10. Univ. Lille, CHU Lille, CNRS, Inserm, Institut Pasteur de Lille, UMR9020 – UMR-S 1277 - Canther, F-59000 , Lille, France
  11. Department of Pulmonology and Thoracic Oncology, Antwerp University Hospital (UZA), Edegem, Belgium
  12. Dr Rosell Oncology Institute, Dexeus University Hospital, QuironSalud Group, Barcelona, Spain
  13. Department of Medical Oncology, National Taiwan University Cancer Center, Taipei, Taiwan
  14. Section of Hematology-Oncology, Department of Medicine, Samsung Medical Center Sungkyunkwan University School of Medicine, Seoul, South Korea
  15. Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China
  16. Medical Oncology, Department of Thoracic Cancer, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, Liaoning, China
  17. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Thoracic Oncology, Peking University Cancer Hospital and Institute, Beijing, China
  18. Global Medical Affairs, Merck Healthcare KGaA, Darmstadt, Germany
  19. Global Patient Safety, Merck Healthcare KGaA, Darmstadt, Germany
  20. Department of Biostatistics, Merck Healthcare KGaA, Darmstadt, Germany
  21. Global Clinical Development, Merck Healthcare KGaA, Darmstadt, Germany
  22. Thoracic Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA , Weill Cornell Medical College, New York, NY, USA

Aim: Tepotinib, a MET TKI, is approved for the treatment of METex14 skipping NSCLC. Here we report analysis of all patients with METex14 skipping in the Phase II VISION study (Cohort A: >2-years’ follow-up; confirmatory Cohort C: >9-months’ follow-up); data cut-off February 20, 2022.

Methods:  Patients with advanced METex14 skipping NSCLC, received tepotinib 500 mg (450 mg active moiety) once daily. Primary endpoint was objective response by IRC using RECIST v1.1. Pre-planned exploratory analysis of brain lesions was conducted by IRC using RANO-BM criteria.

Results: Patients in Cohorts A+C (N=313) had a median age of 72.0 years (range 41–94), 49.2% were male, 47.6% had smoking history, 80.5% had adenocarcinoma histology and 73.8% had ECOG PS 1.

Treatment-naïve patients (1L; overall, n=164) had an ORR of 56.1%; median duration of response (mDOR), progression-free survival (mPFS), and overall survival (mOS) were 46.8, 12.6 and 19.1 months, respectively. Among 111 1L patients enrolled via tissue biopsy (T+), ORR was 56.8% with mDOR, mPFS, and mOS of 46.8, 16.3 and 25.9 months, respectively.   

Previously treated patients (overall [n=149] and T+ [n=97]) had an objective response rate (ORR) of 45.0% and 49.5%, with mDOR of 12.4 and 10.2 months, mPFS of 13.7 and 11.5 months, and mOS of 20.9 and 20.4 months.

Intracranial (i) disease control rate in patients evaluable by RANO-BM (n=43) was 88.4% with iPFS of 20.9 months.

Treatment-related adverse events (TRAEs) occurred in 91.7% of patients (Grade ≥3 34.2%); including (≥15%) peripheral edema (any grade/Grade ≥3: 66.5/10.9%), nausea (23.3/0.6%), hypoalbuminemia (23.0/3.2%), diarrhea (22.4/0.3%), and increased blood creatinine (21.7/0.6%). Permanent discontinuation due to TRAEs occurred in 14.7% of patients.

Conclusion:  In VISION, the largest clinical trial of a MET inhibitor in METex14 skipping NSCLC, tepotinib showed robust and durable efficacy, particularly in 1L patients, and promising intracranial activity was observed.