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

Area of Science:

• Immunotherapy
• Oncology
• Pharmacology

Background:

• Checkpoint inhibitor (CPI) resistance remains a challenge in advanced non-small-cell lung cancer (NSCLC).
• Novel therapeutic strategies targeting multiple immune checkpoints are under investigation.

Purpose of the Study:

• To evaluate the safety, tolerability, pharmacodynamics, pharmacokinetics, and preliminary antitumor activity of rilvegostomig, a novel anti-PD-1/TIGIT bispecific antibody.
• To determine the recommended Phase II dose (RP2D) of rilvegostomig in CPI-experienced patients with advanced or metastatic NSCLC.

Main Methods:

• A first-in-human, multicenter, Phase I/II, open-label study (NCT04995523) enrolled CPI-experienced patients with PD-L1-positive advanced/metastatic NSCLC.
• Part A involved dose escalation of intravenous rilvegostomig (70-1500 mg Q3W) in 51 patients.
• Part B included dose expansion (n=32) at the determined RP2D of 750 mg Q3W.

Main Results:

• No dose-limiting toxicities were observed; the RP2D was established as 750 mg Q3W.
• Treatment-emergent adverse events (TEAEs) occurred in 90.4% of patients; 18.1% experienced immune-mediated AEs.
• At the RP2D, the objective response rate was 5.6%, median progression-free survival (PFS) was 3.8 months, and 12-month PFS was 11.9%.

Conclusions:

• Rilvegostomig demonstrated evidence of clinical efficacy in a pretreated population.
• The drug exhibited favorable tolerability with a low rate of treatment discontinuation.
• These findings support further investigation of rilvegostomig in CPI-naïve NSCLC patients.