As reported in the Journal of Clinical Oncology by Hanna et al, the 2-year follow-up of the expansion cohort in a phase I/Ib trial indicates persistent benefit of first-line ficerafusp alfa plus pembrolizumab in patients with PD-L1–positive recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC).
Ficerafusp alfa is a novel bifunctional immunoglobulin G1 anti-EGFR antibody fused to the transforming growth factor-β (TGF-β) receptor II ectodomain that selectively neutralizes TGF-β in the tumor microenvironment.
Study Details
In the multicenter study, 42 patients with a PD-L1 combined positive score of ≥ 1 were enrolled between February 2022 and April 2023. They received at least one dose of the study drug, with 39 being included in the efficacy analysis. Patients received ficerafusp alfa at 1,500 mg once every week plus pembrolizumab at 200 mg once every 3 weeks. Among the 39 patients evaluable for efficacy, 11 had human papillomavirus (HPV)-positive disease and 28 had HPV-negative disease.
Key Findings
Median follow-up was 26.3 months. Grade 3 treatment-related adverse events occurred in 19 (45%) of 42 patients, most commonly anemia (14%) and acneiform dermatitis (12%); 1 patient had a grade 4 treatment-related adverse event. Treatment-related adverse events led to discontinuation of ficerafusp alfa in 5 patients (12%). No treatment-related deaths were reported.
Among 28 evaluable patients with HPV-negative disease, objective response was observed in 15 (54%, 95% confidence interval [CI] = 34%–73%), including complete response in 6 (21%). Median duration of response was 21.7 months (95% CI = 6.0 months to not evaluable). Median progression-free survival was 9.9 months (95% CI = 4.4–22.7 months). Median overall survival was 21.3 months (95% CI = 9.9 months to not evaluable).
Among 11 evaluable patients with HPV-positive disease, objective response was observed in 3 (27%, 95% CI = 6%–61%), including complete response in 2 (18%). Median duration of response was not evaluable. Median progression-free survival was 2.0 months (95% CI = 1.0–10.0 months). Median overall survival was 16.4 months (95% CI = 2.6–25.7 months).
The investigators concluded: “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.”
Glenn J. Hanna, MD, of Center for Head and Neck Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, is the corresponding author for the Journal of Clinical Oncology article.
DISCLOSURE: The study was supported by Bicara Therapeutics. For full disclosures of the study authors, visit ascopubs.org.
