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

purposeRilvegostomig, an anti-PD-1/T cell immunoreceptor with Ig and immunoreceptor tyrosine-based inhibitory motif domain 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 cell death ligand-1 (PD-L1)-positive advanced or metastatic non-small cell lung cancer (NSCLC). PATIENTS AND

methodsIn part A, patients (n = 51) received intravenous rilvegostomig at escalating doses of 70, 210, 750, and 1,500 mg, once every 3 weeks. 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.

resultsIn 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 once every 3 weeks. At data cutoff (April 21, 2025), 90.4% of patients had treatment-emergent adverse events (AE) of any grade, 18.1% of patients had investigator-assessed immune-mediated AEs, and 54.2% had treatment-related AEs (TRAE), including 8.4% with grade 3 TRAEs, with few treatment-related discontinuations (2.4%). At the RP2D, the objective response rate was 5.6%, the 6-month disease control rate was 31.5%, the median progression-free survival (PFS) was 3.8 months, and the 12-month PFS was 11.9%.

conclusionsThe 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 to E of the study, which assess safety and efficacy in CPI-naïve patients with nonsquamous and/or squamous NSCLC with a PD-L1 tumor proportion score of ≥1% or ≥50%.