Oral Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2022

Tepotinib with an EGFR-tyrosine kinase inhibitor (TKI) in patients with EGFR-mutant MET-amplified NSCLC: A case series (#83)

Wei-Sen Lam 1 , Xiuning Le 2 , Anna Eisert 3 , Ulrike Himpe 4 , Charlotte De Bondt 5 , Julien Mazieres 6 , Iacopo Petrini 7 , Lye Mun Tho 8 , Azura Ahmad 9 , Yin Kwan Jeannie Chik 10 , Wai Chung Kirsty Lee 11 , Tsung-Ying Yang 12 , Te-Chun Hsia 13 , Kirti Joshi 14 , Louise Young 15 , Karin Berghoff 16 , Soetkin Vlassak 17 , Niki Karachaliou 18 , Anthonie van der Wekken 19
  1. Fiona Stanley Hospital, Murdoch, Western Australia, Australia
  2. Department of Thoracic Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
  3. Department of Internal Medicine, Center for Integrated Oncology , Aachen Bonn Cologne Duesseldorf, University Hospital of Cologne, Cologne, Germany
  4. Department of Pulmonary Diseases, AZ Delta, Roselare, Belgium
  5. Department of Thoracic Oncology, Antwerp University Hospital, Antwerp, Belgium
  6. CHU de Toulouse, Universite Paul Sabatier, Toulouse, France
  7. Unit of Respiratory Medicine, Department of Critical Area and Surgical, Medical and Molecular Pathology, University Hospital Pisa, Pisa, Italy
  8. Department of Oncology, Pantai Hospital Kuala Lumpur, Kuala Lumpur, Malaysia
  9. Beacon Hospital, Selangor, Malaysia
  10. Department of Clinical Oncology, Queen Elizabeth Hospital , Hong Kong
  11. Department of Clinical Oncology, Prince of Wales Hospital, Hong Kong
  12. Division of Chest Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
  13. China Medical University Hospital, Taichung City, Taiwan
  14. Global Development Operations, Merck Healthcare KGaA, Darmstadt, Germany
  15. Oncology, Merck Healthcare Pty Ltd, an affiliate of Merck KGaA, Macquarie Park, Australia
  16. Global Patient Safety, Merck Healthcare KGaA, Darmstadt, Germany
  17. Global Medical Affairs, Merck N.V.-S.A, an afilliate of Merck KGaA, -, Belgium
  18. Global Clinical Development, Merck Healthcare KGaA, Darmstadt, Germany
  19. Department of Pulmonary Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

Aims: MET amplification (METamp) is a mechanism of acquired resistance to EGFR-TKIs. Herein, we present a case series highlighting the clinical activity of tepotinib (a potent, highly selective MET-TKI) + EGFR-TKI (gefitinib and/or osimertinib) in patients with EGFR-mutant METamp NSCLC.

Methods: Early access to tepotinib has been provided through compassionate use. Cases include patients with NSCLC and acquired resistance to EGFR-TKIs due to METamp who received tepotinib outside of a clinical trial (500 mg [450 mg active moiety] once daily; first dose before October 2021) plus an EGFR-TKI.

Results: Twelve cases of patients with EGFR-mutant METamp NSCLC, who received tepotinib plus an EGFR-TKI, are presented (five patients received treatment in second line, three in third line, and four in fourth or later line). Patients were aged 47–86 years, five were Asian, eight were female, three had smoking history, and all had adenocarcinoma histology. METamp was detected by tissue and liquid biopsy in ten and two patients, respectively. In seven patients detected by FISH, MET gene copy number ranged from 5.5–33.4 and MET:CEP7 ratio from 1.8–15.1.

Nine patients received tepotinib plus osimertinib, two patients received tepotinib plus gefitinib, and one patient received both combinations sequentially. The treatment duration ranged from 1.3 to 13.8 months. At the time of data collection, treatment was ongoing in four patients. Eleven patients had clinical benefit per the treating physician’s assessment, of whom eight were considered to have a partial response. Of 12 patients with adverse events (AEs) considered related to tepotinib, seven had edema. Three patients had Grade 3 AEs; no Grade 4 or 5 tepotinib-related AEs were reported.

Conclusions: The combination of tepotinib plus EGFR-TKIs showed promising clinical activity for patients with METamp NSCLC who have progressed on previous EGFR-TKIs, including those with several lines of prior treatment.