Ficerafusp Alfa (BCA101) With Pembrolizumab for Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: Two-Year Results of an Expansion Cohort of a Phase I/Ib Trial

PURPOSE: Patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) have a poor prognosis, particularly those with human papillomavirus (HPV)-negative disease, in which elevated epidermal growth factor receptor and transforming growth factor-β impair tumor penetration of immune cells and lessen immunotherapy responses. METHODS: We present results from an expansion cohort of a first-in-human phase I/Ib trial (ClinicalTrials.gov identifier: NCT04429542) evaluating first-line treatment with ficerafusp alfa 1,500 mg once every week in combination with pembrolizumab 200 mg once every 3 weeks administered intravenously in patients with R/M HNSCC overexpressing PD-L1 (combined positive score ≥1). The primary end point was safety. Secondary end points included objective response rate (ORR), progression-free survival (PFS), duration of response (DOR), and overall survival (OS). RESULTS: Between February 2022 and April 2023, 42 patients received ≥1 dose of study drug and 39 were included in the efficacy-evaluable set (≥1 postbaseline scan). The median follow-up was 26.3 months. Nineteen of 42 patients (45%) had a grade 3 treatment-related adverse event (TRAE), and one (2%) had a grade 4 TRAE. The most common grade ≥3 TRAEs were anemia (14%) and acneiform dermatitis (12%). In efficacy-evaluable patients with HPV-negative (n = 28) or HPV-positive (n = 11) tumors, confirmed ORRs were 54% (complete response in 21%) and 27%, respectively. In the HPV-negative subgroup, median DOR was 21.7 months (95% CI, 6.0 to not estimable [NE]), median PFS was 9.9 months (95% CI, 4.4 to 22.7), and median OS was 21.3 months (95% CI, 9.9 to NE). CONCLUSION: Ficerafusp alfa plus pembrolizumab demonstrated favorable safety and tolerability with promising antitumor activity in the first-line treatment of R/M HNSCC, particularly in those with HPV-negative tumors.