JTO Clinical and Research Reports (Jan 2022)

A Phase 1b Study of Telisotuzumab Vedotin in Combination With Nivolumab in Patients With NSCLC

  • D. Ross Camidge, MD, PhD,
  • Fabrice Barlesi, MD, PhD,
  • Jonathan W. Goldman, MD,
  • Daniel Morgensztern, MD,
  • Rebecca Heist, MD, MPH,
  • Everett Vokes, MD,
  • Eric Angevin, MD, PhD,
  • David S. Hong, MD,
  • Igor I. Rybkin, MD,
  • Minal Barve, MD,
  • Todd M. Bauer, MD,
  • Angelo Delmonte, MD,
  • Martin Dunbar, DrPH,
  • Monica Motwani, PhD,
  • Apurvasena Parikh, PhD,
  • Elysa Noon, PhD,
  • Jun Wu, MD,
  • Vincent Blot, PhD,
  • Karen Kelly, MD

Journal volume & issue
Vol. 3, no. 1
p. 100262

Abstract

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Introduction: Telisotuzumab vedotin (Teliso-V) is an anti-c-Met–directed antibody-drug conjugate that has exhibited antitumor activity as monotherapy in NSCLC. Its potential activity combined with programmed cell death protein-1 inhibitors has not been previously evaluated. Methods: In a phase 1b study (NCT02099058), adult patients (≥18 y) with advanced NSCLC received combination therapy with Teliso-V (1.6, 1.9, or 2.2 mg/kg, every 2 wk) plus nivolumab (3 mg/kg, 240 mg, or per locally approved label). The primary objective was to assess safety and tolerability; secondary objectives included the evaluation of antitumor activity. Results: As of January 2020, a total of 37 patients received treatment with Teliso-V (safety population) in combination with nivolumab; 27 patients (efficacy population) were c-Met immunohistochemistry–positive. Programmed death-ligand 1 (PD-L1) status was evaluated in the efficacy population (PD-L1–positive [PD-L1+]: n = 15; PD-L1–negative [PD-L1–]: n = 9; PD-L1–unknown: n = 3). The median age was 67 years and 74% (20 of 27) of patients were naive to immune checkpoint inhibitors. The most common any-grade treatment-related adverse events were fatigue (27%) and peripheral sensory neuropathy (19%). The pharmacokinetic profile of Teliso-V plus nivolumab was similar to Teliso-V monotherapy. The objective response rate was 7.4%, with two patients (PD-L1+, c-Met immunohistochemistry H-score 190, n = 1; PD-L1–, c-Met H-score 290, n = 1) having a confirmed partial response. Overall median progression-free survival was 7.2 months (PD-L1+: 7.2 mo; PD-L1–: 4.5 mo; PD-L1–unknown: not reached). Conclusions: Combination therapy with Teliso-V plus nivolumab was well tolerated in patients with c-Met+ NSCLC with limited antitumor activity.

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