Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2026

Overcoming tumor penetration barriers via dual EGFR/TGF-β inhibition: A multicenter, randomized, double-blind, phase 2/3 study of ficerafusp alfa (BCA101) or placebo with pembrolizumab in first-line recurrent or metastatic (R/M) PD-L1-positive, HPV-negative head and neck squamous cell carcinoma (HNSCC): The FORTIFI-HN01 study (146155)

Marcin Dzienis 1 , Bella Nguyen 2 , Jenny Lee 3 4 , Fiona Day 5 , Danny Rischin 6 , Melvin Chua 7 , Wan Teck Darren Lim 8 9 , Ang Choon Seong 10 , Makoto Tahara 11 , Nuttapong  Ngamphaiboon 12 , Wan Zamaniah WI 13 , Anshul Agarwal 14 , Jonathan Hayman 15 , Chris Nguyen 15 , Zhao Yang 15 , Bhumsuk  Keam 16 17
  1. Department of Medical Oncology, Gold Coast University Hospital, Gold Coast, Queensland, Australia
  2. Department of Medical Oncology, Fiona Stanley Hospital, Perth, Australia
  3. Macquarie University, Sydney, NSW, Australia
  4. Chris O'Brien Lifehouse, Sydney, NSW, Australia
  5. Department of Medical Oncology, Calvary Mater Newcastle, Newcastle, Australia
  6. Department of Medical Oncology, Peter MacCallum Cancer, Melbourne, Australia
  7. Division of Radiation Oncology, National Cancer Centre Singapore, Singapore
  8. Division of Medical Oncology, National Cancer Centre Singapore, Singapore
  9. Institute of Molecular and Cell Biology, A*STAR, Singapore
  10. Sarawak General Hospital, Sarawak, Malaysia
  11. Division of Head and Neck Medical Oncology, The National Cancer Center Hospital East, Kashiwa, Japan
  12. Department of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
  13. Department of Clinical Oncology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia
  14. Department of Medical Oncology, Nirmal Hospital Pvt. Ltd., Surat, Gujarat, India
  15. Bicara Therapeutics, Boston, MA, USA
  16. Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea
  17. Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea

Background: HPV-negative HNSCC is an aggressive cancer with poor prognosis, characterized by an EGFR- and TGF-β-driven fibrotic, immune-hostile tumor microenvironment (TME) that impairs therapeutic and immune penetration. Ficerafusp alfa, a first-in-class bifunctional antibody targeting EGFR and TGF-β, is designed to remodel the fibrotic TME and enable tumor penetration. In a phase 1/1b trial (NCT04429542) in patients with first-line R/M HNSCC, ficerafusp alfa plus pembrolizumab demonstrated a 54% objective response rate, a 21.7-month median duration of response, and a manageable safety profile. FORTIFI-HN01 (NCT06788990) is an ongoing randomized, double-blind, placebo-controlled, phase 2/3 trial investigating ficerafusp alfa plus pembrolizumab versus placebo plus pembrolizumab in first-line, R/M, PD-L1-positive, HPV-negative HNSCC.

 

Trial Design: Eligible patients have histologically confirmed R/M HNSCC with primary tumor in the oral cavity, larynx, or hypopharynx, or HPV-negative (tested centrally) oropharyngeal carcinoma, and no prior systemic therapy for R/M disease. Patients must have a PD-L1–positive tumor (CPS ≥1), measurable disease per RECIST 1.1, and ECOG performance status of 0 or 1. Patients in Phase 2 were randomized 1:1:1 to ficerafusp alfa 750mg once weekly (QW), ficerafusp alfa 1500mg QW, or placebo, each combined with pembrolizumab (200mg IV every 3 weeks; up to 35 cycles). Through integrated analysis of safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy, ficerafusp alfa 1500mg QW was selected as the optimal biological dose. Phase 3 is enrolling with 2:1 randomization to ficerafusp alfa (1500mg IV QW) or placebo (IV QW), each combined with pembrolizumab, with treatment until disease progression or unacceptable toxicity. Tumor assessments are performed every 6 weeks in the first year and every 9 weeks thereafter. Dual primary endpoints are objective response rate (blinded independent central review) per RECIST 1.1 and overall survival. Secondary endpoints include safety, additional efficacy measures, and patient-reported outcomes. The trial is actively recruiting, with a planned enrollment of ~650 patients.