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

Abstract

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.

Keywords: Antibody-drug conjugate; Nivolumab; Non–small cell lung cancer; Telisotuzumab vedotin; c-Met.

Figure 1

Best percentage reduction in (A) target lesions and (B) Kaplan-Meier estimates of PFS. (A) Responses were reported at the same visit as the best percentage change from the baseline assessment. (B) Three efficacy-assessable patients did not have a postbaseline scan owing to the withdrawal of consent (n = 1) and discontinuation owing to AE (n = 2). AE, adverse event; CI, confidence interval; NR, not reached; PD-L1, programmed death-ligand 1; PD-L1+, PD-L1–positive; PD-L1–, PD-L1–negative; PD-L1–unk, PD-L1–unknown; PFS, progression-free survival.