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).

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.

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%).

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.