Frontline Ficerafusp Alfa Plus Pembrolizumab Shows Promise in HPV-Negative HNSCC

Head and Neck Cancer |
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The combination of ficerafusp alfa (BCA101) and pembrolizumab (Keytruda) elicited responses when used as a frontline regimen in patients with human papillomavirus (HPV)–negative recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), according to updated interim data from the phase 1/1b KEYNOTE-E28 trial (NCT04429542) presented during the 2025 ASCO Annual Meeting.1

At a data cutoff date of March 20, 2025, the confirmed objective response rate (ORR) in patients with HPV-negative, relapsed or metastatic HNSCC that had a PD-L1 combined positive score (CPS) of at least 1 (n = 28) was 54%. The ORR (confirmed or unconfirmed) was 64%, which comprised a complete response rate of 21%.1,2 Notably, 80% of those who responded experienced at least 80% tumor shrinkage. The disease control rate with the regimen was 89%.

The median time to response was 1.4 months, and the median duration of response (DOR) was 21.7 months. Moreover, 79% of patients continued to respond for at least 6 months, 65% for at least 12 months, and 57% for at least 18 months. The median progression-free survival (PFS) was 9.9 months. At a median follow-up of 25.2 months, the median overall survival (OS) was 21.3 months; the 2-year OS rate was 46%. In those with a CPS ranging from 1 to 19, the median OS was 22.0 months; in those with a CPS of 20 or higher, the median OS was 20.6 months.

“Ficerafusp alfa plus pembrolizumab is a promising first-line regimen in HPV-negative, recurrent/metastatic head and neck cancer that demonstrates high [ORR], deep and durable responses, and prolonged OS,” Christine H. Chung, MD, of Moffitt Cancer Center, said in a presentation of the data.

Diving Into the Trial

The early-phase trial enrolled patients with first-line recurrent or metastatic HNSCC who were negative for HPV. Patients could have had cancer in the oral cavity, oropharynx, larynx, or hypopharynx. They were required to have a CPS of at least 1.

Study participants were given 1500 mg of ficerafusp alfa on days 1, 8, and 15 plus 200 mg of pembrolizumab on day 1 every 21 days.

When looking at demographics and baseline characteristics in the safety set (n = 30), the median age was 63 years (range, 31-84), and most were male (63%) and had an ECOG performance status of 1 (63%). Primary sites of disease included oropharynx (27%), oral cavity (47%), hypopharynx (13%), and larynx (13%). Half of patients had a CPS ranging from 1 to 19, and half had a CPS of 20 or higher. Thirty percent of patients had locoregional-only disease, and 47% had locoregional and distant metastatic disease. Sum of target lesions was over 50 mm (47%) or over 70 mm (27%) in diameter.

Safety Spotlight

The combination had a favorable toxicity profile, with no new safety signals. Any treatment-emergent adverse effects (TEAEs) were experienced by 93% of patients; grade 3 TEAEs occurred in 47% of patients, and grade 4 TEAEs were recorded in 3%.

The most common TEAEs reported in at least 20% of patients that were related to ficerafusp alfa included dermatitis acneiform (all grade, 77%; grade 3, 13%), pruritus (53%; 0%), anemia (43%; 20%), hypomagnesemia (43%; 0%), fatigue (37%; 3%), dry skin (30%; 0%), hypophosphatemia (27%; 0%), hypokalemia (27%; 0%), stomatitis (23%; 0%), and nausea (20%; 0%).

Looking at the Limitations and Next Steps

“These results are from a multicenter, single-arm, dose-expansion cohort with 2-year follow-up of all patients,” Chung noted regarding limitations of the data.

The phase 2/3 FORTIFI-HN01 study (NCT06788990) is now enrolling patients with HPV-negative, recurrent or metastatic HNSCC to further assess the benefits of ficerafusp alfa plus pembrolizumab as first-line treatment.3

References

1. Chung CH, Hanna GJ, Zandberg DP, et al. Ficerafusp alfa with pembrolizumab in patients recurrent or metastatic head and neck squamous cell carcinoma: updated results from an expansion cohort of an open-label, multicenter, phase 1/1b trial. J Clin Oncol. 2025;43(suppl 16_:6017. doi:10.1200/JCO.2025.43.16_suppl.6017
2. Bicara Therapeutics demonstrates deep and durable responses with ficerafusp alfa plus pembrolizumab in 1L HPV-negative R/M HNSCC at ASCO 2025. News release. Bicara Therapeutics, Inc. June 1, 2025. Accessed June 1, 2025. https://ir.bicara.com/news-releases/news-release-details/bicara-therapeutics-demonstrates-deep-and-durable-responses
3. 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). ClinicalTrials.gov. Updated May 30, 2025. Accessed June 1, 2025. https://clinicaltrials.gov/study/NCT06788990