A Phase 1a/b Open‑Label, Dose‑Escalation Study of Etigilimab Alone or in Combination with Nivolumab in Patients with Locally Advanced or Metastatic Solid Tumors.

Purpose: TIGIT is a co-inhibitory receptor of T cell and natural killer cell activity. Targeting TIGIT with or without PD-1/PD-L1 checkpoint inhibition may enhance anti-tumor immunity. Patients and Methods: This Phase 1a/b trial was a first-in-human, open label, multicenter, dose escalation and expansion study in patients with locally advanced or metastatic solid tumors. Using 3+3 design, patients underwent 14-day treatment cycles with anti-TIGIT antibody etigilimab alone (phase 1a; 0.3, 1.0, 3.0, 10.0, 20.0 mg/kg intravenously) or in combination with anti-PD-1 antibody nivolumab (phase 1b; 3.0, 10.0, 20.0 mg/kg etigilimab and 240 mg nivolumab). Primary objective was safety and tolerability. Results: Thirty-three patients were enrolled (Phase 1a, n=23; Phase 1b, n=10). There were no DLTs. MTD for single and combination therapy was not determined; maximum administered dose was 20 mg/kg. The most commonly reported adverse events (AEs) were rash (43.5%), nausea (34.8%) and fatigue (30.4%) in Phase 1a and decreased appetite (50.0%), nausea (50.0%) and rash (40%) in Phase 1b. Six patients experienced Grade {greater than or equal to}3 treatment-related AEs. In phase 1a, 7 patients (30.0%) had stable disease. In Phase 1b, 1 patient had a partial response; 1 patient had prolonged stable disease of nearly 8 months. Median progression-free survival was 56.0 days (Phase 1a) and 57.5 days (Phase 1b). Biomarker correlative analyses demonstrated evidence of clear dose-dependent target engagement by etigilimab. Conclusion: Etigilimab had an acceptable safety profile with preliminary evidence of clinical benefit alone and in combination with nivolumab and warrants further investigation in clinical trials.