A Phase II Study of Telisotuzumab Vedotin in Patients With c–MET-positive Stage IV or Recurrent Squamous Cell Lung Cancer (LUNG-MAP Sub-study S1400K, NCT03574753)

Saiama N. Waqar, Mary W. Redman, Susanne M. Arnold, Fred R. Hirsch, Philip C. Mack, Lawrence H. Schwartz, David R. Gandara, Thomas E. Stinchcombe, Natasha B. Leighl, Suresh S. Ramalingam, Saloni H. Tanna, Ryan S. Raddin, Katherine Minichiello, Jeffrey D. Bradley, Karen Kelly, Roy S. Herbst, Vassiliki A. Papadimitrakopoulou

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Introduction: Lung-MAP S1400K was designed to evaluate the response to telisotuzumab vedotin, an antibody-drug conjugate targeting c-MET, in patients with c-MET–positive squamous cell carcinoma (SCC). Patients and Methods: Patients with previously treated SCC with c-MET–positive tumors (H score ≥ 150, Ventana SP44 assay) were enrolled into 2 cohorts: Cohort 1 (immune checkpoint inhibitor-naive) and Cohort 2 (immune checkpoint inhibitor refractory). Telisotuzumab vedotin 2.7 mg/kg was administered intravenously every 3 weeks until disease progression or unacceptable toxicity. Response assessments were performed every 6 weeks. The primary endpoint was response by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Secondary endpoints included progression-free survival, overall survival, response within cohort, duration of response, and toxicities. Interim analysis was planned after 20 evaluable patients, with ≥ 3 responses needed to continue enrollment. Results: Forty-nine patients (14% of screened patients) were assigned to S1400K, 28 patients enrolled (15 in Cohort 1 and 13 in Cohort 2), and 23 were eligible. S1400K closed on December 21, 2018 owing to lack of efficacy. Two responses (response rate of 9%; 95% confidence interval, 0%-20%) were reported in cohort 1 (1 complete and 1 unconfirmed partial response), whereas 10 patients had stable disease, with a disease control rate of 52%. The median overall and progression-free survival was 5.6 and 2.4 months, respectively. There were 3 grade 5 events (2 pneumonitis, in Cohort 2, and 1 bronchopulmonary hemorrhage, in Cohort 1). Conclusion: Telisotuzumab vedotin failed to meet the pre-specified response needed to justify continuing enrollment to S1400K. Pneumonitis was an unanticipated toxicity observed in patients with SCC.

Original languageEnglish
Pages (from-to)170-177
Number of pages8
JournalClinical Lung Cancer
Volume22
Issue number3
DOIs
StatePublished - May 2021

Bibliographical note

Funding Information:
Dr Waqar reports grants from 1 UM1 CA186704-01 outside of this submitted work, and research support to Washington University School of Medicine from AbbVie outside of this submitted work. Dr Arnold reports grants from AbbVie for other clinical trials, outside the submitted work. Dr Hirsch has received research grants from AbbVie for laboratory studies at University of Colorado (through University of Colorado), laboratory support (through University of Colorado) from Merck, Biodesix, Amgen, Rain Therapeutics, and Mersana, and has also participated in scientific advisory boards for AbbVie, BMS, Merck, Genentech, Lilly, Novartis, and AstraZeneca. Dr Mack reports personal fees from AstraZeneca and Amgen outside the submitted work. Dr Schwartz has served as a DSMB member for independent review of response assessment imaging studies blinded to treatment and outcomes for Merck, Boehringer Ingelheim, Hoffman La Roche, and Novartis outside this submitted work. Dr Gandara has served on the advisory board for AbbVie, outside of this submitted work. Dr Ramalingam reports personal fees for advisory board from AbbVie, Amgen, BMS, Genentech, Lilly, Takeda, and Loxo, and grants from AstraZeneca, Merck, and Tesaro outside the submitted work. Dr Kelly reports research grants and personal fees for advisory board from AbbVie outside this submitted work, personal fees from AstraZeneca for participation in advisory board and DMC meeting, research grant (drug only) and personal fees for advisory board from Bristol-Myers Squibb Canada, research funding (drug only) and personal fees for DMC meeting from Genentech, personal fees for advisory board from Pfizer outside the submitted work. Dr Herbst reports personal fees from Abbvie Pharmaceuticals, ARMO Biosciences, Biodesix, Bristol-Myers Squibb, EMD Serrano, Genmab, Halozyme, Heat Biologics, Loxo Oncology, Nektar, Novartis, Pfizer, Sanofi, Seattle Genetics, Shire PLC, Spectrum Pharmaceuticals, Symphogen, Tocagen, Tesaro, IMAB Biopharma, Immunocore, Midas Health Analytics, Mirati Tnerapeutics, and Takeda; and grants and personal fees from AstraZeneca, Merck and Company, Eli Lilly and Company, Genentech/Roche; personal fees for scientific advisory board from Infinity Pharmaceuticals, Neon Therapeutics, and NextCure; and personal fees for board membership (non-executive/ independent) from Junshi Pharmaceuticals outside the submitted work. Dr Papadimitrakopoulou is currently an employee of Pfizer, Inc, and has received personal fees for Advisory Board from Abbvie, and personal fees from Eli Lilly, Novartis, Merck, Nektar Therapeutics, Janssen, Araxes, Arrys Therapeutics, Clovis Oncology, Exelixis, Gritstone, Ideaya, Leeds Biolabs, Loxo Oncology, Takeda, Tesaro, and TRM Oncology outside this submitted work, and grants from Eli Lilly, Novartis, Merck, Nektar Therapeutics, Janssen Checkmate, and Incyte outside the submitted work. The remaining authors have stated that they have no conflicts of interest.The Lung-MAP trial was supported in part by National Institutes of Health/National Cancer Institute grants CA180888, CA180819, CA180820, CA180821, CA180868, CA189997, CA189858, CA189873, CA180828, CA189830, CA189971, CA189952, CA189804, CA239767, CA189808, and CA189958, and by AbbVie through the Foundation for the National Institutes of Health, in partnership with Friends of Cancer Research.

Funding Information:
The Lung-MAP trial was supported in part by National Institutes of Health / National Cancer Institute grants CA180888 , CA180819 , CA180820 , CA180821 , CA180868 , CA189997 , CA189858 , CA189873 , CA180828 , CA189830 , CA189971 , CA189952 , CA189804 , CA239767 , CA189808 , and CA189958 , and by AbbVie through the Foundation for the National Institutes of Health , in partnership with Friends of Cancer Research.

Publisher Copyright:
© 2020 Elsevier Inc.

Keywords

  • Antibody-drug conjugate
  • Lung-MAP
  • Squamous cell carcinoma
  • Telisotuzumab vedotin
  • c-MET

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

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