Bicara Therapeutics has enrolled the first patients in FORTIFI-HN01, marking a significant advancement in the treatment landscape for head and neck squamous cell carcinoma (HNSCC). This pivotal Phase 2/3 trial will evaluate ficerafusp alfa, a novel bifunctional antibody, in combination with pembrolizumab for first-line treatment of recurrent/metastatic HNSCC.
Novel Therapeutic Approach
Ficerafusp alfa represents a pioneering approach in oncology, combining an EGFR-directed monoclonal antibody with a TGF-β binding domain. This dual-targeting mechanism aims to simultaneously inhibit cancer cell growth and overcome immunosuppression in the tumor microenvironment.
"This is a key milestone for Bicara and represents our transition into a late-stage clinical development company," said Dr. David Raben, Chief Medical Officer of Bicara Therapeutics. "Supported by encouraging interim Phase 1/1b data, which demonstrated durable and clinically meaningful anti-tumor activity with ficerafusp alfa in combination with pembrolizumab, FORTIFI-HN01 will evaluate the potential of ficerafusp alfa as a first-in-class treatment option for patients with advanced head and neck squamous cell carcinoma."
Trial Design and Patient Population
FORTIFI-HN01 is designed as a global, randomized, double-blinded, placebo-controlled study with approximately 650 participants. The trial specifically excludes patients with HPV-positive oropharyngeal squamous cell carcinoma and requires participants to have a PD-L1 CPS score of one or greater, with no prior systemic therapy in the recurrent/metastatic setting.
The study's primary endpoints include overall response rate based on RECIST v1.1 and overall survival, with data potentially supporting both accelerated and full approval pathways. Secondary endpoints encompass progression-free survival and duration of response.
Addressing Critical Unmet Needs
Dr. John Kaczmar of Medical University of South Carolina Hollings Cancer Center highlighted the urgent need for innovative treatments: "Head and neck squamous cell carcinoma is a cancer of growing concern across the world. Incidence is rising, yet survival rates remain low, particularly for patients with HPV-negative disease."
The global burden of HNSCC is expected to reach one million new cases annually by 2030. Approximately 80% of recurrent/metastatic HNSCC cases are HPV-negative, presenting with severe morbidities including fatal tumor bleeding, intense pain, and significant weight loss.
Clinical Implications
The development of ficerafusp alfa represents a strategic approach to addressing the complex challenges of HNSCC treatment. By targeting both EGFR and TGF-β pathways, the therapy aims to provide a more comprehensive treatment strategy for patients with limited options.
The trial's design reflects Bicara's commitment to expediting the development of novel treatments while maintaining rigorous scientific standards. Success in this trial could potentially establish a new standard of care for first-line treatment of recurrent/metastatic HNSCC, particularly benefiting patients with HPV-negative disease who currently face limited therapeutic options.
