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

作者：Kristoffer Staal Rohrberg, Mariana Brandão, Eduardo Castañón Álvarez, Enriqueta Felip, Eelke Hiddo Gort, T. Jeroen N. Hiltermann, Hiroki Izumi, Dong‐Wan Kim, Sang‐We Kim, Luis G Paz-Ares, Benjamin J. Solomon, Egbert Frederik Smit, Els Wauters, Tatsuya Yoshida, Amal Ayyoub, Huifang Chen, Steve Colebrook, Negar Hamidi, Michael Kuziora, KyoungSoo Lim, Ikbel Achour, Moritz Drachsler, Djuro Karanovic, Nelson Liu, Byoung Chul Cho · 发表于：Clinical Cancer Research · 年份：2026 · DOI：10.1158/1078-0432.ccr-26-0333 · 被引用次数：1 · 研究领域：Lung Cancer Research Studies、Peptidase Inhibition and Analysis、HER2/EGFR in Cancer Research

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 obse...