Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2023

Treatment sequencing in the VISION study of tepotinib in patients with MET exon 14 (METex14) skipping NSCLC (#199)

Frank Griesinger 1 , Marina Garassino 2 , Enriqueta Felip 3 , Hiroshi Sakai 4 , Xiuning Le 5 , Remi Veillon 6 , Egbert Smit 7 , Jo Raskin 8 , Michael Thomas 9 , Myung-Ju Ahn 10 , Soetkin Vlassak 11 , Stephanie Gasking 12 , Rolf Bruns 13 , Andreas Johne 14 , Paul K. Paik 15
  1. Department of Hematology and Oncology, Pius-Hospital, University of Oldenburg, Oldenburg, Germany
  2. Department of Medicine, Section of Hematology/Oncology, Knapp Center for Biomedical Discovery, The University of Chicago, IL, USA
  3. Department of Oncology, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain
  4. Department of Thoracic Oncology, Ageo Central General Hospital, Ageo, Japan
  5. Department of Thoracic Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
  6. CHU Bordeaux, Service des Maladies Respiratoires, Bordeaux, France
  7. Department of Pulmonary Diseases, Leiden University Medical Center, Leiden, The Netherlands
  8. Department of Pulmonology and Thoracic Oncology, Antwerp University Hospital (UZA), Edegem, Belgium
  9. Thoraxklinik and National Center for Tumor Diseases at Heidelberg University Hospital, Heidelberg, Germany, Translational Lung Research Center Heidelberg (TLRC-H), Member of the German Center for Lung Research (DZL)
  10. Section of Hematology-Oncology, Department of Medicine, Samsung Medical Center Sungkyunkwan University School of Medicine, Seoul, South Korea
  11. Global Medical Affairs, Merck N.V.-S.A., Overijse, Belgium, an affiliate of Merck KGaA
  12. Merck Healthcare Pty. Ltd., Macquarie Park, Australia, an affiliate of Merck KGaA
  13. Department of Biostatistics, Merck Healthcare KGaA, Darmstadt, Germany
  14. Global Clinical Development, Merck Healthcare KGaA, Darmstadt, Germany
  15. Thoracic Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

Background: Tepotinib is a MET TKI approved for METex14 skipping NSCLC. We report treatment sequencing prior/post tepotinib of immunotherapy (IO), chemotherapy (CT) and METi (post only) in VISION (data cut-off: Feb 20, 2022).

Methods: Patients with advanced/metastatic METex14 skipping NSCLC received 500 mg (450 mg active moiety) tepotinib QD. Primary endpoint was objective response (RECIST 1.1) by IRC. Prior/post tepotinib treatment was investigator’s choice; outcomes were reported per investigator.

Results: Of 313 patients (median age 72), 164 were treatment‑naïve (median age 74) and 149 pre-treated (median age 70.8). Among pre-treated patients, the most common 1L regimens prior to enrolling in VISION were platinum-CT without IO (58%), IO monotherapy (23%) and IO-CT (13%).

Across all those prior 1L regimens, median treatment duration was 4 months (IQR 1.8–7.3), with an ORR of 24.8%, mDOR of 6.0 months, and mPFS of 4.0 months. 1L treatment outcomes with tepotinib were greatly improved (ORR, 56.1%; mDOR, 46.4 months; mPFS, 12.6 months).  

Overall, 265 patients (84.7%) discontinued tepotinib; 124 patients (46.8%) received subsequent treatment. 48 patients received subsequent METi (crizotinib, n=20; capmatinib, n=15; bozitinib, n=4; tepotinib, n=3; amivantamab, n=3; cabozantinib, n=3; other, n=4; different METi in subsequent lines, n=4). 31 patients received subsequent METi immediately after tepotinib (1L, n=11; 2L+, n=20). BOR across all subsequent METi was 3 PR (all after a break in METi treatment), 11 SD; longest mDOR and mPFS were 4.0 and 2.5 months, respectively. Outcomes with subsequent CT/IO were comparable to prior CT/IO as well as those in literature.

Conclusions: Robust and durable efficacy, particularly in the 1L setting, support early use of tepotinib in the treatment sequence. Almost half of this elderly population received subsequent treatment, higher than the 20%–30% reported for 1L CT/IO IPSOS trial in elderly patients (median age 75). METi treatment sequencing analyses are ongoing.