Expansion cohort of a multicenter phase 1-1b trial of first-line ficerafusp alfa plus pembrolizumab for R/M HNSCC: two-year results

Patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) have a poor prognosis, particularly those with HPV-negative disease, in which elevated EGFR aand TGF-β impair tumor penetration of immune cells and lessen immunotherapy responses. A multicenter first-in-human phase 1-1b trial evaluated first-line ficerafusp alfa 1500 mg once every week in combination with pembrolizumab 200 mg once every three weeks in patients with R/M HNSCC overexpressing PD-L1 (combined positive score ≥ 1. The primary endpoint was safety. Two-year results of an expansion cohort of the trial have now been published. A total of 42 patients received treatment and 39 were included in the efficacy-evaluable set. The median follow-up was 26.3 months. Nineteen of 42 patients (45%) had a grade 3 treatment-related adverse events, and one had a grade 4 TRAE. Among efficacy-evaluable patients with HPV-negative (n=28) or HPV-positive (n=11) tumors, confirmed objective response rates were 54% (complete response in 21%) and 27%, respectively. In the HPV-negative subgroup, the median duration of response was 21.7 months (95% CI 6.0-NE), median progression-free survival was 9.9 months (4.4-22.7), and median overall survival was 21.3 months (9.9-NE). The authors conclude that ficerafusp alfa plus pembrolizumab demonstrated favorable safety and tolerability with promising antitumor activity in first-line treatment of R/M HNSCC.