Bicara Therapeutics Updates Interim Phase 1/1b Data on Ficerafusp Alfa in 1L HPV-negative Recurrent/Metastatic HNSCC

Bicara Therapeutics has unveiled promising interim data from its ongoing clinical study of ficerafusp alfa (BCA101), a novel bifunctional antibody, at the 3rd Hawaii Global Summit on Thoracic Malignancies. This antibody integrates two validated targets: an EGFR-directed monoclonal antibody and a domain binding to TGF-β. The study is investigating the efficacy of ficerafusp alfa in combination with pembrolizumab in patients with HPV-negative, recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC).

The Phase 1/1b clinical trial results showcased that the combination therapy exhibited a 64% overall response rate (ORR), 18% complete response (CR) rate, and a median progression-free survival (mPFS) of 9.8 months in the targeted patient group. Notably, these figures reflect a substantial improvement over the historical 19% ORR observed with pembrolizumab monotherapy, currently the standard of care in R/M HNSCC.

Dr. David Raben, Chief Medical Officer of Bicara Therapeutics, emphasized the significance of these findings, highlighting the durable responses seen in patients with at least a year of follow-up. The data suggests that ficerafusp alfa, combined with pembrolizumab, could potentially establish a new chemotherapy-free standard of care for HPV-negative first-line R/M HNSCC.

Dr. Claire Mazumdar, CEO of Bicara Therapeutics, explained that ficerafusp alfa's mechanism involves simultaneously inhibiting EGFR and TGF-β signaling, targeting cancer cell survival and immunosuppressive pathways within the tumor microenvironment. This dual action is believed to contribute to the observed durable responses and survival benefits. The company plans to advance to a pivotal Phase 2/3 trial in frontline R/M HNSCC, excluding HPV-positive patients, and explore ficerafusp alfa's potential in other squamous cell tumor types.

The updated interim data, as of April 2024, included 39 evaluable patients with a PD-L1 combined positive score (CPS) of ≥1. Among these, 28 were HPV-negative and 11 were HPV-positive. For the overall study population, the ORR was 54%, with a 15% CR rate. Particularly in the HPV-negative subgroup, the ORR was 64%, with an 18% CR rate. The median progression-free survival for this group was 9.8 months, and both the median duration of response and overall survival have not yet been reached.

Head and neck squamous cell carcinomas (HNSCC) are significant malignancies that arise from the mucosal epithelium in areas such as the oral cavity, pharynx, and larynx. These cancers are common globally, with an incidence projected to reach one million new cases annually by 2030. A substantial portion of HNSCC cases are HPV-negative, often resulting from carcinogenic exposures like tobacco smoke. These tumors are prone to local recurrence and are associated with severe symptoms, underscoring the need for effective, durable treatments.

Ficerafusp alfa represents a cutting-edge approach in cancer treatment, designed to inhibit both EGFR and TGF-β directly at the tumor site. This strategy aims to curb tumor growth while enhancing the immune cells' cytolytic activity against the tumor. Bicara Therapeutics is currently evaluating ficerafusp alfa in combination with pembrolizumab for HPV-negative R/M HNSCC, advanced squamous non-small cell lung cancer, and squamous cancer of the anal canal. Additionally, it is being tested as a monotherapy for cutaneous squamous cell carcinoma.

Bicara Therapeutics is dedicated to developing bifunctional therapies that combine tumor-targeting antibodies with tumor microenvironment modulators. Their lead product, ficerafusp alfa, exhibits potential across multiple tumor types, aiming to deliver enhanced therapeutic outcomes directly at the tumor site.