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INSIGHT 2: a phase II study of tepotinib plus osimertinib in MET-amplified NSCLC and first-line osimertinib resistance

F Smit E 1 , Dooms C 2 , Raskin J 3 , Nadal E 4 , Tho LM 5 , Le X 6 Show all authors , Mazieres J 7 , S Hin H 8 , Morise M 9 , W Zhu V 10 , Tan D 11 , H Holmberg K 12 , Ellers-Lenz B 13 , Adrian S 14 , Brutlach S 15 , Schumacher KM 14 , Karachaliou N 14 , Wu YL 16

Affiliations 

  • 1 Department of Thoracic Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands
  • 2 Department of Respiratory Diseases & Respiratory Oncology Unit, University Hospitals Leuven, Leuven, Belgium
  • 3 Department of Pulmonology & Thoracic Oncology, Antwerp University Hospital (UZA), Edegem, Belgium
  • 4 Department of Medical Oncology, Catalan Institute of Oncology, L'Hospitalet, Barcelona, Spain
  • 5 Department of Oncology, Pantai Hospital, Kuala Lumpur, Malaysia
  • 6 Department of Thoracic Head & Neck Medical Oncology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA
  • 7 CHU de Toulouse, Institut Universitaire du Cancer, Toulouse, France
  • 8 Hospital Tengku Ampuan Afzan, Pahang, Malaysia
  • 9 Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan
  • 10 University of California Irvine, Chao Family Comprehensive Cancer Center, Orange, CA, USA
  • 11 Division of Medical Oncology, National Cancer Centre Singapore, Singapore
  • 12 EMD Serono Research & Development Institute, Inc., MA, USA, an affiliate of Merck KGaA
  • 13 Department of Biostatistics, Merck Healthcare KGaA, Darmstadt, Germany
  • 14 Global Clinical Development, Merck Healthcare KGaA, Darmstadt, Germany
  • 15 Late Stage Development Operations, Merck Healthcare KGaA, Darmstadt, Germany
  • 16 Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China
Future Oncol, 2022 Mar;18(9):1039-1054.
PMID: 34918545 DOI: 10.2217/fon-2021-1406

Abstract

MET amplification (METamp), a mechanism of acquired resistance to EGFR tyrosine kinase inhibitors, occurs in up to 30% of patients with non-small-cell lung cancer (NSCLC) progressing on first-line osimertinib. Combining osimertinib with a MET inhibitor, such as tepotinib, an oral, highly selective, potent MET tyrosine kinase inhibitor, may overcome METamp-driven resistance. INSIGHT 2 (NCT03940703), an international, open-label, multicenter phase II trial, assesses tepotinib plus osimertinib in patients with advanced/metastatic EGFR-mutant NSCLC and acquired resistance to first-line osimertinib and METamp, determined centrally by fluorescence in situ hybridization (gene copy number ≥5 and/or MET/CEP7 ≥2) at time of progression. Patients will receive tepotinib 500 mg (450 mg active moiety) plus osimertinib 80 mg once-a-day. The primary end point is objective response, and secondary end points include duration of response, progression-free survival, overall survival and safety. Trial registration number: NCT03940703 (clinicaltrials.gov).

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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