Ficerafusp Alfa/Pembrolizumab Demonstrates Clinically Meaningful Activity in Metastatic HNSCC

David Raben, MD

Ficerafusp alfa (BCA101) in combination with pembrolizumab (Keytruda) demonstrated clinically meaningful anti-tumor activity for the first-line treatment of patients with HPV-negative recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), according to findings from the phase 1/1b KEYNOTE-E28 trial (NCT04429542).¹

Updated interim data from the dose expansion cohort were presented during the third Hawaii Global Summit on Thoracic Malignancies, demonstrating that at an April 2024 data cutoff, patients with HPV-negative disease (n = 28) achieved an overall response rate (ORR) of 64%, including an 18% complete response (CR) rate; 3 of the responses were unconfirmed. The median progression-free survival (PFS) was 9.8 months. At a minimum follow-up of 12 months, the median duration of response (DOR) and overall survival (OS) were not yet reached.

“Data from our ongoing phase 1/1b clinical trial reflected a substantial increase over the historical 19% ORR observed in a phase 3 trial with pembrolizumab monotherapy, the current standard of care in recurrent/metastatic HNSCC,” David Raben, MD, chief medical officer of Bicara Therapeutics, stated in a press release.¹ “Now with at least a year of follow-up on this cohort, it is encouraging to see a number of patients experience durable responses with the CR and median PFS data that have emerged.

“We believe these data indicate that ficerafusp alfa in combination with pembrolizumab may become a new chemotherapy-free standard of care treatment for HPV-negative first-line recurrent/metastatic HNSCC.”

The bifunctional antibody ficerafusp alfa is an EGFR-directed monoclonal antibody that contains a TGF-β-binding domain. The agent is designed to inhibit tumor proliferation and restore cytolytic activity of the local immune cells.

KEYNOTE-E28 is an open-label study evaluating ficerafusp alfa both as monotherapy and within a combination therapy in patients with EGFR-driven advanced solid tumors. To be eligible for the study, patients needed to have measurable disease per RECIST v1.1 and an ECOG performance status of 1 or less.

The study consisted of a dose escalation part for ficerafusp alfa monotherapy and dose expansion part for ficerafusp alfa plus pembrolizumab. The respective parts enrolled patients with advanced solid tumors who are refractory to or without a standard of care option; patients with HNSCC or squamous cell carcinoma of the anal canal refractory to or without a standard of care option were also enrolled.²

Safety, tolerability, and incidence of dose-limiting toxicities all served as primary end point for the trial. Secondary end points included ORR, clinical benefit rate, PFS, DOR, OS, and pharmacokinetic parameters.

Additional findings from KEYNOTE-E28 showed that efficacy-evaluable patients with a PD-L1 combined positive score of at least 1 (n = 39), 11 of whom were HPV-positive, achieved an ORR of 54%; this included a 15% CR rate. Notably, 10 patients experienced a 100% reduction in target lesions.¹

Investigators noted that the tolerability profile of ficerafusp alfa plus pembrolizumab was favorable. The most common any-grade treatment-related adverse effects in the overall population included acneiform rash (76%), fatigue (43%), and hypophosphatemia (38%). Most instances of acneiform rash were of grade 1 or 2 severity.

“Ficerafusp alfa has the potential to exert potent anti-tumor activity by simultaneously blocking both cancer cell–intrinsic EGFR survival and proliferation, as well as immunosuppressive TGF-β signaling within the tumor microenvironment to lead to durable responses and improved survival,” Claire Mazumdar, PhD, MBA, chief executive officer of Bicara Therapeutics, added in the press release.¹

“Given these data, we intend to initiate a pivotal phase 2/3 trial of ficerafusp alfa in combination with pembrolizumab in frontline recurrent/metastatic HNSCC excluding HPV-positive patients. We also remain excited about the potential of ficerafusp alfa to expand into other populations of HNSCC patients and across other squamous cell tumor types where there is a strong biologic rationale for the dual inhibition of both EGFR and TGF-β.”

References

1. Bicara Therapeutics Reports Updated Interim Phase 1/1b Data of Ficerafusp Alfa (BCA101) in 1L HPV-negative Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma (HNSCC). News release. Bicara Therapeutics. June 27, 2024. Accessed June 27, 2024. https://www.bicara.com/bicara-therapeutics-reports-updated-interim-phase-1-1b-data-of-ficerafusp-alfa-bca101-in-1l-hpv-negative-recurrent-metastatic-head-and-neck-squamous-cell-carcinoma-hnscc/
2. Study of Safety and Tolerability of BCA101 Monotherapy and in Combination Therapy in Patients With EGFR-driven Advanced Solid Tumors. ClinicalTrials.gov. Updated June 27, 2024. Accessed June 27, 2024. https://clinicaltrials.gov/study/NCT04429542