Less-Frequent Ficerafusp Alfa Dosing Strategy Yields Durable Responses in Metastatic HNSCC

First-line ficerafusp alfa (BCA101) dosed at 2000 mg every 2 weeks in combination with pembrolizumab (Keytruda) generated deep and durable responses and had a well-tolerated safety profile in patients with recurrent or metastatic human papillomavirus (HPV)–negative head and neck squamous cell carcinoma (HNSCC), according to preliminary findings from an exploratory expansion cohort of a phase 1b trial (NCT04429542) presented at the 2026 Multidisciplinary Head and Neck Cancers Symposium.^1,2

The efficacy and safety profiles of pembrolizumab plus ficerafusp alfa at the investigated dose and schedule (n = 27) were consistent with the known profiles of the combination with ficerafusp alfa dosed at 1500 mg weekly in this patient population. At a data cutoff date of December 16, 2025, the confirmed overall response rate (cORR) was 48%, and the complete response (CR) rate was 26%. Furthermore, 77% of responders achieved at least 80% tumor shrinkage. The median time to response was 1.6 months. Among patients with response at 24 weeks (n = 11), 73% had achieved at least 80% tumor shrinkage at this time point. Additional efficacy findings continue to mature.

“Results from this alternative dosing cohort, including rapid, deep and durable responses, a consistent safety profile, and sustained TGF-β neutralization in [patients with] first-line HPV-negative recurrent or metastatic HNSCC, reinforce the strength of ficerafusp alfa’s differentiated mechanism of action,” David Raben, MD, chief medical officer of Bicara Therapeutics, stated in a news release.¹ “TGF-β inhibition is established quickly and sustained with less frequent dosing [and simultaneously maintains] deep and durable responses, creating a compelling opportunity to pursue a loading and maintenance regimen for ficerafusp alfa. We remain confident that ficerafusp alfa uniquely enables both meaningful tumor penetration and long‑term benefit, and we are committed to advancing dosing options that strengthen both patient experience and outcomes.”

What is important to note about the design of the dose-expansion cohort of the phase 1 trial of ficerafusp alfa in HNSCC?

The dose-expansion portion of this trial enrolled patients with HPV-negative, first-line, recurrent or metastatic HNSCC of the oral cavity, oropharynx, larynx, or hypopharynx who had a PD-L1 combined positive score (CPS) of at least 1 and an ECOG performance status of 0 or 1.² Ficerafusp alfa plus pembrolizumab is being assessed across 3 dose levels. The data presented at the 2026 Multidisciplinary Head and Neck Cancers Symposium focused on patients who received ficerafusp alfa at 2000 mg every 2 weeks plus pembrolizumab at 400 mg every 6 weeks.

What was the safety profile of ficerafusp alfa at 2000 mg every 2 weeks plus pembrolizumab in HNSCC?

Any-grade treatment-emergent adverse effects (TEAEs) were reported in 97% of patients in this cohort. Grade 3 TEAEs occurred in 53% of patients. The most common grade 3 TEAEs included dermatitis acneiform (10%), anemia (27%), fatigue (3%), stomatitis (10%), pruritus (3%), and nausea (3%). Investigators reported no treatment-related deaths.

What efficacy findings have been previously seen with ficerafusp alfa at 1500 mg weekly in HNSCC?

Data from this phase 1 trial presented at the 2025 ASCO Annual Meeting showed that efficacy-evaluable patients who received ficerafusp alfa at 1500 mg weekly in combination with pembrolizumab (n = 28) achieved a cORR of 54% and a CR rate of 21%.³ The disease control rate was 89%, and 80% of patients experienced a deep response. Additionally, the median duration of response was 21.7 months, the median progression-free survival was 9.9 months, and the median overall survival (OS) was 21.3 months.

Notably, data from this portion of the trial supported the October 2025 FDA breakthrough therapy designation of first-line ficerafusp alfa plus pembrolizumab for the treatment of patients with metastatic or unresectable/recurrent HNSCC whose tumors have a PD-L1 CPS of at least 1, except for HPV-positive oropharyngeal squamous cell carcinoma.⁴

“The FDA designation of breakthrough status underscores the exciting data we’ve seen thus far,” Deborah J. Wong, MD, PhD, of UCLA Health in Los Angeles, California, stated in a previous interview with OncLive®.⁵

What’s next for investigating ficerafusp alfa in HNSCC?

The phase 2/3 FORTIFI-HN01 trial (NCT06788990) is exploring first-line ficerafusp alfa or placebo in combination with pembrolizumab in patients with PD-L1–positive, HPV-negative recurrent or metastatic HNSCC.^2,6 The phase 2 portion of the trial identified the optimal biological dose of ficerafusp alfa to be 1500 mg weekly.² Patients will now be randomly assigned 2:1 to receive ficerafusp alfa at the identified dose plus pembrolizumab at 200 mg every 3 weeks, or pembrolizumab at the same dose and schedule plus weekly placebo. The dual primary end points of the phase 3 portion are ORR and OS.^2,6

References

1. Ficerafusp alfa 2000mg Q2W demonstrates deep, durable responses in 1L R/M HPV-negative HNSCC and supports development of less frequent dosing regimen. News release. Bicara Therapeutics Inc. February 19, 2026. Accessed March 18, 2026. https://ir.bicara.com/news-releases/news-release-details/ficerafusp-alfa-2000mg-q2w-demonstrates-deep-durable-responses
2. Zandberg DP, Kaczmar JM, Sacco AG, et al. Ficerafusp alfa (2000 mg Q2W) and pembrolizumab in HPV-negative first-line recurrent/metastatic head and neck squamous cell carcinoma. Presented at: 2026 Multidisciplinary Head and Neck Cancers Symposium. February 19-21, 2026. Palm Desert, CA. Abstract 3.
3. Chung CH, Hanna GJ, Zandberg DP, et al. Ficerafusp alfa with pembrolizumab in patients with 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
4. Bicara Therapeutics announces ficerafusp alfa granted breakthrough therapy designation by U.S. FDA for 1L HPV-Negative R/M HNSCC. News release. Bicara Therapeutics. October 13, 2025. Accessed March 18, 2026. https://ir.bicara.com/news-releases/news-release-details/bicara-therapeutics-announces-ficerafusp-alfa-granted
5. Doherty K. Ficerafusp alfa plus pembrolizumab shows robust activity in frontline PD-L1+, HPV– HNSCC. OncLive.com. February 9, 2026. Accessed March 18, 2026. https://www.onclive.com/view/ficerafusp-alfa-plus-pembrolizumab-shows-robust-activity-in-frontline-pd-l1-hpv-hnscc
6. 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 March 5, 2026. Accessed March 18, 2026. https://clinicaltrials.gov/study/NCT06788990