Fianlimab, a human lymphocyte activation gene‐3 monoclonal antibody, in combination with cemiplimab: Tumor‐specific expansion cohorts in advanced malignancies

作者：Tae Min Kim, Stephen K. Williamson, Kyriakos P. Papadopoulos, O Hamid, Grace K. Dy, Ray McDermott, Ariel Birnbaum, John M. Kaczmar, Nehal J. Lakhani, D Rischin, Debashis Sarker, Afshin Dowlati, Xin‐Hua Zhu, Jyoti Malhotra, Jean‐Francois Pouliot, Jayakumar Mani, Laura Brennan, Fang Fang, Shuquan Chen, Mark Salvati, Israel Lowy, Ahmed Khaled, Karl D. Lewis, Glenn Kroog, Matthew G. Fury, B Cho · 发表于：Cancer · 年份：2026 · DOI：10.1002/cncr.70396 · 被引用次数：1 · 研究领域：Cancer Immunotherapy and Biomarkers、CAR-T cell therapy research、Immunotherapy and Immune Responses

BACKGROUND: The dose escalation phase of a first-in-human (FIH) study demonstrated acceptable safety and preliminary antitumor activity of fianlimab (anti-lymphocyte activation gene-3 [LAG-3]) as monotherapy and in combination with cemiplimab (anti-programmed cell death-1 [PD-1]). Here, the authors present safety and clinical activity data from the dose-expansion portion of the FIH study in patients with advanced non-small cell lung cancer (NSCLC), clear cell renal cell carcinoma (ccRCC), head and neck squamous cell carcinoma (HNSCC), and cutaneous squamous cell carcinoma (CSCC). METHODS: Anti-PD-1/PD-L1 naive (N) or experienced (E) patients with advanced NSCLC, ccRCC, HNSCC, and CSCC were enrolled in this phase 1 study (NCT03005782). Patients received fianlimab 1600 mg plus cemiplimab 350 mg intravenously every 3 weeks for up to 24 months. The primary end point was the objective response rate (ORR) per RECIST 1.1. RESULTS: Investigator-assessed ORR was 27% in NSCLC-N (four partial responses [PRs]), 7% in NSCLC-E (one PR), 20% in ccRCC-N (three PRs), 7% in ccRCC-E (one PR), 33% in HNSCC-N (five PRs), 7% in HNSCC-E (one PR), and 20% CSCC-E (two complete responses; one PR). The most common treatment-related treatment-emergent adverse events among patients across all cohorts were fatigue (15%), rash (12%), pruritus (10%), infusion-related reaction (10%), and adrenal insufficiency (10%). CONCLUSIONS: Fianlimab plus cemiplimab demonstrated modest clinical efficacy with an acceptab...