Tumor-specific expansion cohorts of a first-in-human phase 1 trial of fianlimab plus cemiplimab for advanced malignancies

The dose escalation phase of a first-in-human study demonstrated acceptable safety and preliminary antitumor activity of fianlimab (anti-LAG-3) as monotherapy and in combination with cemiplimab (anti-PD-1). Results of expansion cohorts of the study have now been published. The cohorts included anti-PD-1/PD-L1 naïve (N) or experienced (E) patients with advanced non-small cell lung cancer (NSCLC), clear cell renal carcinoma (ccRCC), head and neck squamous cell carcinoma (HNSCC), and cutaneous squamous cell carcinoma (CSCC). Patients received fianlimab 1600 mg plus cemiplimab 350 mg intravenously every 3 weeks for up to 24 months. The primary endpoint was investigator-assessed objective response rate (ORR). The ORR was 27% in NSCLC-N, 7% in NSCLC-E, 20% in ccRCC-N, 7% in ccRCC-E, 33% in HNSCC-N, 7% in HNSCC-E, and 20% in CSCC-E. The most common treatment-related adverse events across all cohorts were fatigue (15%), rash (12%), pruritus (10%), infusion-related reaction (10%), and adrenal insufficiency (10%). The authors conclude that fianlimab plus ipilimuab demonstrated modest clinical efficacy with an acceptable safety profile in patients with advanced malignancies; mostly in treatment-naïve patients.