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
Mené sur 42 patients atteints d'un carcinome épidermoïde de la tête et du cou récidivant ou métastatique, cet essai de phase I/IB examine la sécurité du ficérafusp alfa (un anticorps ciblant EGFR et TGF-alpha) en combinaison avec le pembrolizumab puis évalue l'efficacité de cette combinaison du point de vue du taux de réponse objective, de la survie sans progression, de la durée de la réponse et de la survie globale
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.
Journal of Clinical Oncology , article en libre accès, 2026