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

Kim, TM; Williamson, SK; Papadopoulos, KP; Hamid, O; Dy, GK; McDermott, R; Birnbaum, A; Kaczmar, JM; Lakhani, N; Rischin, D; Sarker, D; Dowlati, A; Zhu, XH; Malhotra, J; Pouliot, JF; Mani, J; Brennan, L; Fang, F; Chen, S; Salvati, M; Lowy, I; Khaled, A; Lewis, KD; Kroog, G; Fury, MG; Cho, BC

Author(s): Kim, TM; Williamson, SK; Papadopoulos, KP; Hamid, O; Dy, GK; McDermott, R; Birnbaum, A; Kaczmar, JM; Lakhani, N; Rischin, D; Sarker, D; Dowlati, A; Zhu, XH; Malhotra, J; Pouliot, JF; Mani, J; Brennan, L; Fang, F; Chen, S; Salvati, M; Lowy, I; Khaled, A; Lewis, KD; Kroog, G; Fury, MG; Cho, BC;
Details: Publication Year 2026-05-01,Volume 132,Issue #9,Page e70396
Journal Title: Cancer
Publication Type: Research article
Abstract: 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 acceptable safety profile in patients with advanced malignancies across several tumor types mostly in treatment-naive patients. Further investigation is warranted.
Publisher: Wiley
Keywords: Humans; Male; Female; Middle Aged; Aged; *Antibodies, Monoclonal, Humanized/administration & dosage/adverse effects; Lymphocyte Activation Gene 3 Protein; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use/adverse; effects/administration & dosage; Adult; Carcinoma, Non-Small-Cell Lung/drug therapy; *Neoplasms/drug therapy; Lung Neoplasms/drug therapy; Carcinoma, Renal Cell/drug therapy; Aged, 80 and over; Squamous Cell Carcinoma of Head and Neck/drug therapy; Lag‐3; Pd‐1; advanced malignancies; cemiplimab; fianlimab
Department(s): Medical Oncology
Publisher's Version: https://doi.org/10.1002/cncr.70396
Open Access at Publisher's Site: https://doi.org/10.1002/cncr.70396
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2026-05-19 02:35:05

Last Modified: 2026-05-19 02:35:24