Rilvegostomig for Metastatic Non–Small Cell Lung Cancer: A First-In-Human Phase I/II Clinical Study

PURPOSE: Rilvegostomig, an anti-PD-1/TIGIT bispecific antibody, was evaluated in this first-in-human, multicenter, phase I/II, open-label study (NCT04995523) in checkpoint inhibitor (CPI)-experienced patients with programmed death ligand-1 (PD-L1)-positive advanced or metastatic non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: In Part A, patients (n = 51) received intravenous rilvegostomig at escalating doses of 70, 210, 750, and 1500 mg, once every 3 weeks (Q3W). Dose expansion in Part B (n = 32) was initiated once the recommended phase II dose (RP2D) was declared in Part A. Safety, tolerability, pharmacodynamics, pharmacokinetics and preliminary antitumor activity were evaluated. RESULTS: In Part A no dose-limiting toxicities were observed, the maximum tolerated dose was not reached and the rilvegostomig RP2D for dose expansion in Part B was 750 mg Q3W. At data cut-off (April 21, 2025), 90.4% of patients had treatment-emergent adverse events (TEAEs) of any grade, 18.1% of patients had investigator-assessed immune-mediated AEs, and 54.2% had treatment-related AEs (TRAEs), including 8.4% with grade 3 TRAEs, with few treatment-related discontinuations (2.4%). At the RP2D, objective response rate was 5.6%, 6-month disease control rate was 31.5%, median progression-free survival (PFS) was 3.8 months, and 12-month PFS was 11.9%. CONCLUSIONS: The evidence of clinical efficacy in a pretreated population, favorable tolerability and low rate of treatment discontinuation observed in Parts A and B support further evaluation of rilvegostomig in Parts C-E of the study, which assess safety and efficacy in CPI-naïve patients with nonsquamous and/or squamous NSCLC with PD-L1 tumor proportion score ≥1% or ≥50%.