FDA Grants Breakthrough Therapy Designation to Ficerafusp Alfa in Head and Neck Cancer

The U.S. Food and Drug Administration (FDA) has granted breakthrough therapy designation to ficerafusp alfa in combination with Keytruda (pembrolizumab) for the first line treatment of patients with metastatic or unresectable, recurrent head and neck squamous cell carcinoma whose tumors express PDL1 with combined positive score of at least 1, with the exception of human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma.

The development was announced in a news release issued by Bicara Therapeutics, the clinical-stage biopharmaceutical company behind ficerafusp alfa. The designation, according to the news release, underscores the growing reconition of HPV-negative head and neck squamous cell carcinoma as a distinct clinical indication, and one that has particularly poor outcomes with limited therapeutic options.

“This recognition highlights the urgent unmet need for patients with HPV-negative [metastatic or unresectable, recurrent head and neck squamous cell carcinoma],” said Dr. David Raben, Chief Medical Officer of Bicara Therapeutics, in a statement in the news release. “It also reinforces our conviction that depth and durability of response, driven by ficerafusp alfa's ability to synergize with [Keytruda] and enable tumor penetration, are key to achieving long-term clinical benefit.”

The breakthrough therapy designation, according to the news release, was supported by the results of multiple phase 1 and 1b dose cohorts that were evaluating the treatment combination in the first-line setting among patients with HPV-negative metastatic or unresectable, recurrent head and neck squamous cell carcinoma, with data presented at the 2025 American Society of Clinical Oncology Annual Meeting demonstrating a median duration of response of 21.7 months and a median overall survival of 21.3 months with a favorable safety and tolerability profile.

“[Breakthrough therapy designation] provides external validation of the importance of ficerafusp alfa’s best-in-disease potential, and solidifies the foundation for our ongoing pivotal trial, FORTIFI-HN01,” said Claire Mazumdar, Chief Executive Officer of Bicara Therapeutics. “We look forward to working closely with the FDA to bring this therapy to patients as quickly as possible.”

It was announced earlier this year that the first patients had been enrolled in the FORTIFI-HN01 study, a phase 2/3 clinical trial of ficerafusp alfa in combination with Keytruda among this patient population.

“Incidence is rising, yet survival rates remain low, particularly for patients with HPV-negative disease, underscoring the urgent need for innovative treatment options,” Dr. John Kaczmar of Medical University of South Carolina Hollings Cancer Center, said in a news release issued at the time. “I’m encouraged by the early signs of clinical activity in these patients we have seen treated with ficerafusp alfa and hopeful it will help address this area of significant unmet need.”

The trial, according to its listing on clinicaltrials.gov, is actively recruiting patients at 50 locations in the United States, Canada, Australia and New Zealand. It plans to enroll approximately 650 patients, and has an estimated primary completion date of April 2028, with an expected study completion date of July 2029, according to the listing.

Breakthrough Therapy designation, as the FDA explains on its website, is a process that is designed to expedite the development and review of drugs that are intended to treat a serious condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapy on a clinically significant endpoint.

Ficerafusp alfa, according to the news release, is a first-in-class bifunctional antibody that is designed to drive tumor penetration by breaking barriers in the tumor microenvironment that have challenged the treatment of multiple solid tumor cancers, and combines two targets, an EGFR-directed monoclonal antibody with a domain that binds to human transforming growth factor beta.

References

1. “Bicara Therapeutics Announces Ficerafusp Alfa Granted Breakthrough Therapy Designation by U.S. FDA for 1L HPV-Negative R/M HNSCC,” news release; https://www.globenewswire.com/news-release/2025/10/13/3165460/0/en/Bicara-Therapeutics-Announces-Ficerafusp-Alfa-Granted-Breakthrough-Therapy-Designation-by-U-S-FDA-for-1L-HPV-Negative-R-M-HNSCC.html
2. “Ficerafusp Alfa Trial Begins for Recurrent/Metastatic Head and Neck Cancer,” CURE; https://www.curetoday.com/view/ficerafusp-alfa-trial-begins-for-recurrent-metastatic-head-and-neck-cancer
3. “Breakthrough Therapy,” FDA; https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/breakthrough-therapy
4. “FORTIFI-HN01: A Study of Ficerafusp Alfa (BCA101) or Placebo in Combination With Pembrolizumab in First-Line PD-L1-pos, R or M HNSCC (FORTIFI-HN01);” https://www.clinicaltrials.gov/study/NCT06788990#study-overview

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