478TiP - A phase II, multicenter, four-cohort study of oral cMET inhibitor capmatinib (INC280) in patients with EGFR wild-type, advanced NSCLC who have rece...

Date 20 December 2015
Event ESMO Asia 2015 Congress
Session Poster presentation 2
Topics Anti-Cancer Agents & Biologic Therapy
Non-Small-Cell Lung Cancer, Metastatic
Presenter Jürgen Wolf
Citation Annals of Oncology (2015) 26 (suppl_9): 125-147. 10.1093/annonc/mdv532
Authors J. Wolf1, M. Hochmair2, J.G. Kattan3, M.K. Ang4, E.B. Garon5, H.J.M. Groen6, R. Heist7, K. Ohashi8, E. Felip9, N. Reguart10, R. Garcia Campelo11, R. Soo12, L. Paz-Ares13, F. de Marinis14, E.F. Smit15, M. Giovannini16, M. Squires17, X. Cui18, Y. Zhang19, D. Tan20
  • 1Klinik I Für Innere Medizin, University Hospital Cologne, 50937 Köln - Köln/DE
  • 2Dept. Of Respiratory Oncology, Otto Wagner Spital, Vienna/AT
  • 3Dept. Of Hematology/oncology, Hotel Dieu de France Hospital, 1107 2020 - Beirut/LB
  • 4Dept. Of Medical Oncology, National Cancer Center, Singapore/SG
  • 5David Geffen School Of Medicine, UCLA - School of Medicine, Los Angeles/US
  • 6Dept. Of Pulmonary Diseases, University Hospital Groningen (UMCG), 9700 RB - Groningen/NL
  • 7Dept. Of Medicine, Massachusetts General Hospital, Boston/US
  • 8Dept. Of Respiratory Medicine, Okayama University Hospital, 700-8558 - Okayama/JP
  • 9Dept. Of Oncology, Vall d'Hebron University Hospital, Barcelona/ES
  • 10Dept. Of Medical Oncology, Hospital Clinic y Provincial de Barcelona, 08036 - Barcelona/ES
  • 11Lung Cancer And Thoracic Tumors Dept., Hospital Universitario a Coruna - a Corunac, A Coruna/ES
  • 12Dept. Of Haematology-oncology, National University Health System, National University Cancer Institute, Singapore, 119228 - Singapore/SG
  • 13Dept. Of Medical Oncology, Hospital Universitario 12 De Octubre, Madrid/ES
  • 141 Unità Operativa Di Pneumologia Oncologica, Istituto Europeo di Oncologia, 20141 - Milano/IT
  • 15Dept. Of Thoracic Oncology, Het Nederlands Kanker Instituut Antoni van Leeuwenhoek (NKI-AVL), Amsterdam/NL
  • 16Oncology Clinical Development, Novartis Pharma AG, Basel/CH
  • 17Oncology Correlative Sciences, Novartis Pharma AG, 4002 - Basel/CH
  • 18Oncology Clinical Pharmacology, Novartis Pharmaceuticals Corporation, East hanover/US
  • 19Biostatistics, Novartis Pharmaceuticals Corporation, East Hanover/US
  • 20Dept. Of Medical Oncology, National Cancer Center, 169610 - Singapore/SG

Abstract

Background

Amplification of cMET leading to oncogenic signaling occurs in ≈4% of non-small cell lung cancer (NSCLC) cases. Mutations in cMET leading to exon 14 deletion (cMETΔex14) are also an actionable target in NSCLC. Capmatinib (INC280) is a potent and selective cMET inhibitor that has shown strong evidence of antitumor activity in an ongoing Phase I study in patients (pts) with EGFR wild-type (WT) advanced NSCLC harboring cMET dysregulation, including high-level cMET amplification (fluorescence in situ hybridization [FISH] gene copy number [GCN] ≥5), and cMETΔex14.

Trial design

This multicenter Phase II four-cohort study (ClinicalTrials.gov identifier NCT02414139) was designed to confirm the clinical activity of capmatinib in pretreated pts with advanced NSCLC according to cMET amplification and cMETΔex14. Eligible pts (≥18 years of age, Eastern Cooperative Oncology Group Performance Status 0–1) must have ALK-negative, EGFR-WT (for activating mutations including exon 19 deletion, and L858R mutation) stage IIIB/IV NSCLC (any histology), and have received 1–2 prior lines of therapy for advanced disease (no prior cMET inhibitor). Centrally assessed cMET amplification and mutation status will be used to assign pts to one of four cohorts (≈69 pts each; N ≈ 276): 1: cMET GCN ≥6 2: cMET GCN ≥4 and <6 3: cMET GCN <4 4: cMETΔex14 mutation regardless of GCN Capmatinib 400 mg tablets will be administered twice daily on a continuous dosing schedule 12 hours apart. Primary and key secondary objectives are to evaluate overall response rate (ORR) and duration of response (DOR), respectively (assessed by blinded independent review). Other secondary objectives include investigator-assessed ORR, DOR, time to response, disease control rate, progression-free survival, safety, and pharmacokinetics. Enrollment is ongoing.

Clinical trial identification

EUDRACT 2014-003850-15

Disclosure

J. Wolf: Advisory boards (compensated) and lecture fees: AstraZeneca, BMS, Boehringer-Ingelheim, MSD, Clovis, Novartis, Pfizer, Roche. E.B. Garon: funds to institution for research sponsored by AstraZeneca, Bristol Myers Squibb, Eli Lilly, Heat, Genentech, Merck, Novartis, Pfizer. H.J.M. Groen: Advisory Board: Pfizer, MSD, Eli Lilly. R. Heist: consulting: Boehringer Ingelheim; research funding (to institution, not to myself): Genentech, Millenium, Debiopharm, Novartis, GSK, Celgene, Abbvie, Sanofi, Incyte, Mirati, Peregrine, Exelixis. E. Felip: Advisory Board: Eli Lilly, Pfizer, Roche, Boehringer Ingelheim, BMS, AstraZeneca and Novartis. N. Reguart: Advisory boards: Pfizer, Boehringuer, Roche, Lilly; research sponsored: Boehringuer, Pfizer. R. Soo: Advisory board: Astra-Zeneca, Boehringer Ingelheim, Merck, Novartis, Pfizer, Roche. L. Paz-Ares: Advisory board: Lilly, Pfizer, Novartis, Boehringer, Roche, Astra, Clovis, BMS. E.F. Smit: Advisory boards: Novartis dealing with ceretinib. M. Giovannini: NVS associate and own NVS stocks. M. Squires, Y. Zhang: employee of Novartis. X. Cui: employee of Novartis; stock ownership. D. Tan: Advisory Board: Novartis, Pfizer; research sponsored: Novartis. All other authors have declared no conflicts of interest.