A multicenter, randomized, double-blind, phase 2/3 study of ficerafusp alfa (BCA101) or placebo in combination with pembrolizumab for first-line treatment of PD-L1-positive, recurrent or metastatic head and neck squamous cell carcinoma: The FORTIFI-HN01 study.
Background: HPV-negative head and neck squamous cell carcinoma (HNSCC) is an aggressive disease characterized by high rates of recurrence, metastasis, and resistance to standard treatments. Over 80% of HPV-negative HNSCC cases overexpress TGF-β, a key driver of poor survival and treatment resistance. Ficerafusp alfa, a first-in-class bifunctional antibody, targets epidermal growth factor receptor (EGFR) while neutralizing TGF-β in the tumor microenvironment. In a Phase 1/1b trial (NCT04429542), ficerafusp alfa demonstrated promising efficacy and a manageable safety profile in first-line recurrent/metastatic (R/M) HNSCC. The ongoing FORTIFI-HN01 study (NCT06788990) is a randomized, double-blind, placebo-controlled Phase 2/3 trial designed to assess the efficacy and safety of ficerafusp alfa combined with pembrolizumab versus placebo plus pembrolizumab in patients with PD-L1 positive first-line R/M HPV-negative HNSCC. Methods: Eligible patients must have histologically confirmed R/M HNSCC with primary lesions in the oral cavity, larynx, or hypopharynx, or OPSCC, excluding HPV-positive OPSCC confirmed by central laboratory testing. Additional criteria include no prior systemic therapy for R/M disease, PD-L1 positive tumors (CPS ≥1), measurable disease per RECIST v1.1 assessed by BICR, and ECOG performance status of 0 or 1. The Phase 2 objective is to determine the optimal biological dose (OBD) of ficerafusp alfa through an integrated analysis of safety, tolerability, PK, PD, and efficacy. Subjects will be randomized 1:1:1 to receive high-dose ficerafusp alfa, low-dose ficerafusp alfa, or placebo, each combined with pembrolizumab. Randomization is stratified by PD-L1 CPS (1-19 vs. ≥20) and disease extent (local/regional recurrence only, distant metastasis only, or both). After OBD determination, the trial will transition seamlessly into Phase 3 with a 2:1 randomization (OBD vs. control).Patients will receive pembrolizumab (200 mg i.v. every 3 weeks for up to 35 cycles) and either ficerafusp alfa (1500 mg or 750 mg) or placebo weekly until disease progression or unacceptable toxicity. Tumor imaging will occur every 6 weeks during the first year and every 9 weeks thereafter. The primary endpoints are objective response rate (ORR) per RECIST v1.1 (BICR) and overall survival (OS). Secondary endpoints include safety, additional efficacy measures, and patient-reported outcomes (PROs). The trial is actively recruiting, with a planned enrollment of (NCT06788990).
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Author Details
Renata Ferrarotto
The University of Texas MD Anderson Cancer Center, Houston, TX
Abstract Details
Meeting
2025 ASCO Annual Meeting
Session Type
Poster Session
Session Title
Head and Neck Cancer
Track
Head and Neck Cancer
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