Phase I study of 2- or 3-week dosing of telisotuzumab vedotin, an antibody-drug conjugate targeting c-met, monotherapy in patients with advanced non-small cell lung carcinoma

D. Ross Camidge, Daniel Morgensztern, Rebecca S. Heist, Minal Barve, Everett Vokes, Jonathan W. Goldman, David S. Hong, Todd M. Bauer, John H. Strickler, Eric Angevin, Monica Motwani, Apurvasena Parikh, Zhaowen Sun, Bruce Allen Bach, Jun Wu, Philip B. Komarnitsky, Karen Kelly

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Purpose: Telisotuzumab vedotin (Teliso-V) is an anti-c-Met-directed antibody-drug conjugate. Here, we present safety and efficacy data from a phase I/Ib study of Teliso-V monotherapy evaluated in once every 2 weeks/once every 3 weeks schedules in patients with non-small cell lung cancer (NSCLC). Patients and Methods: During dose escalation, patients received Teliso-V monotherapy intravenously once every 3 weeks (0.15-3.3 mg/kg) or once every 2 weeks (1.6-2.2 mg/kg). The dose-expansion phase enrolled patients with NSCLC and c-Met H-score ≥150 (c-Metþ) or MET amplification/exon 14 skipping mutations. Safety, pharmacokinetics, and efficacy were assessed. Herein, the analysis of patients receiving ≥1.6 mg/kg once every 2 weeks or ≥2.4 mg/kg once every 3 weeks Teliso-V is reported. Results: Fifty-two patients with NSCLC were enrolled and received ≥1.6 mg/kg Teliso-V once every 2 weeks (n ¼ 28) or ≥2.4 mg/kg Teliso-V once every 3 weeks (n ¼ 24). The most common adverse events were fatigue (54%), peripheral neuropathy (42%), and nausea (38%). No dose-limiting toxicities were observed for Teliso-V once every 2 weeks and once every 3 weeks up to 2.2 and 2.7 mg/kg, respectively. The recommended phase II dose was established at 1.9 mg/kg once every 2 weeks and 2.7 mg/kg once every 3 weeks on the basis of overall safety and pharmacokinetics. Forty of 52 patients were c-Metþ (33 nonsquamous, 6 squamous, 1 mixed histology) and were included in the efficacy-evaluable population. Of those, 9 (23%) had objective responses with median duration of response of 8.7 months; median progression-free survival was 5.2 months. Conclusions: Teliso-V monotherapy was tolerated and showed antitumor activity in c-Metþ NSCLC. On the basis of overall safety, pharmacokinetics, and efficacy outcomes, 1.9 mg/kg Teliso-V once every 2 weeks and 2.7 mg/kg once every 3 weeks schedules were selected for further clinical development.

Original languageEnglish (US)
Pages (from-to)5781-5792
Number of pages12
JournalClinical Cancer Research
Volume27
Issue number21
DOIs
StatePublished - Nov 15 2021
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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