Poster Presentation 2025 Joint Meeting of the COSA ASM and IPOS Congress

Long-term outcomes with tepotinib for clinically relevant subgroups of patients with MET exon 14 (METex14) skipping NSCLC in the VISION study: A ≥3-year follow-up (125775)

Stephanie Gasking 1 , Frank Griesinger 2 , Roberto Ferrara 3 , Enriqueta Felip 4 , Egbert F. Smit 5 , Remi Veillon 6 , Xiuning Le 7 , Julien Mazières 8 , Alexis B. Cortot 9 , Jo Raskin 10 , Michael Thomas 11 , Neils Reinmuth 12 , James Chih-Hsin Yang 13 , Myung-Ju Ahn 14 , Jun Zhao 15 , Hiroshi Sakai 16 , Santiago Viteri 17 , Yi-Long Wu 18 , Rolf Bruns 19 , Andreas Johne 20 , Paul K. Paik 21
  1. Merck Healthcare Pty. Ltd., Macquarie Park, Australia, an affiliate of Merck KGaA
  2. Pius-Hospital, University Medicine Oldenburg, Department of Hematology and Oncology, University Department Internal Medicine-Oncology, Oldenburg, Germany
  3. Fondazione IRCCS Istituto Nazionale dei Tumori di Milano Università Vita-Salute San Raffaele Milano, Milan, Italy
  4. Department of Oncology, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain
  5. Department of Pulmonary Diseases, Leiden University Medical Centre, Leiden, The Netherlands
  6. CHU Bordeaux, Service des Maladies Respiratoires, Bordeaux, France
  7. Department of Thoracic Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
  8. CHU de Toulouse, Université Paul Sabatier, Toulouse, France
  9. Univ. Lille, CHU Lille, CNRS, Inserm, Institut Pasteur de Lille, UMR9020 – UMR-S 1277 - Canther, F-59000 Lille, France
  10. Department of Pulmonology and Thoracic Oncology, Antwerp University Hospital (UZA), Edegem, Belgium
  11. Department of Thoracic Oncology, Thoraxklinik, Heidelberg University Hospital and National Center for Tumor Diseases (NCT), NCT Heidelberg, a partnership between DKFZ and Heidelberg University Hospital, Heidelberg, Germany; Translational Lung Research Center Heidelberg (TLRC-H), Member of the German Center for Lung Research (DZL), Heidelberg, Germany
  12. Asklepios Clinics Munich-Gauting, Department of Thoracic Oncology, Gauting, Germany
  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. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Thoracic Oncology, Peking University Cancer Hospital and Institute, Beijing, China
  16. Department of Thoracic Oncology, Ageo Central General Hospital, Saitama, Japan
  17. Instituto Oncológico Dr Rosell, Hospital Universitario Dexeus, Grupo Quiron Salud, Barcelona, Spain
  18. Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China
  19. Clinical Measurement Sciences, Merck Healthcare KGaA, Darmstadt, Germany
  20. Global Clinical Development, Merck Healthcare KGaA, Darmstadt, Germany
  21. Thoracic Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

Background: Tepotinib, an oral MET TKI, showed robust and durable efficacy and safety of tepotinib in patients with ≥3 years follow-up in the VISION study. Here, we report long-term efficacy of tepotinib in clinically relevant subgroups of patients with ≥3 years follow-up (data cut-off: May 20, 2024).

Methods: Patients with advanced/metastatic METex14 skipping NSCLC, detected by tissue (T+) and/or liquid biopsy (L+), received tepotinib 500 mg (450 mg active moiety) QD. Primary endpoint was objective response (RECIST v1.1) by IRC. Subgroup analyses were preplanned; exploratory analysis of brain lesions was conducted using RANO-BM criteria.

Results: Of 313 patients (median age 72.0 years), 41.2% were ≥75 years, 47.6% had smoking history, and 18.2% had brain metastases at baseline; 208 patients were T+ (first line [1L]: 111; second-or-later line [2L+]: 97), 178 were L+ (1L: 95; 2L+: 83), and 73 patients were T+/L+.

T+ patients had an ORR of 54.8% (mDOR, 17.4 months) while L+ patients had an ORR of 51.7% (mDOR, 15.2 months). L+ patients had shorter time-dependent endpoints, potentially due to a higher baseline disease burden.

In patients aged <75 years (n=184), ORR was 55.4% (mDOR, 19.4 months) versus 46.5% (mDOR, 15.7 months) in patients ≥75 years (n=129). Patients with smoking history (n=149) had an ORR of 56.4% (mDOR, 18.0 months), versus 47.4% (mDOR, 20.8 months) in patients without (n=154).

Among 57 patients with baseline brain metastases, systemic ORR was 56.1% (mDOR, 9.0 months), versus 50.8% (mDOR, 19.4 months) in patients without (n=256). In patients with brain tumors as target lesions evaluable by RANO-BM (n=15), intracranial ORR was 66.7% (DCR, 86.7%).

Conclusions: Tepotinib continued to show robust and durable efficacy in patients with ≥3 years follow-up, irrespective of T+/L+ status, age, smoking status, or brain metastases at baseline, consistent with previously reported findings of overall population.