Ficerafusp alfa

Overview

Ficerafusp alfa (also known as BCA101; other code names include FmAb2/FMAB2) is an investigational, bifunctional antibody being developed by Bicara Therapeutics for EGFR-expressing solid tumors, with lead development in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). A pivotal Phase 2/3 trial (FORTIFI‑HN01) in first‑line, PD‑L1–positive, HPV‑negative R/M HNSCC began enrolling in 2025. Early‑phase expansion cohorts have also explored activity in squamous cell carcinoma of the anal canal (SCAC) and cutaneous SCC. (ir.bicara.com)

Mechanism of action

Ficerafusp alfa is an anti‑EGFR IgG1 monoclonal antibody fused to the extracellular domain of TGF‑β receptor II, functioning as a tumor‑targeted TGF‑β “trap.” In preclinical studies it: - Binds EGFR, inhibits proliferation and retains ADCC - Neutralizes TGF‑β in the tumor microenvironment, reduces SMAD signaling, and decreases iTreg differentiation - Enhances cytokine production and augments antitumor activity, including in combination with anti‑PD‑1 therapy

These data support dual blockade of tumor‑intrinsic EGFR signaling and TGF‑β–mediated immunosuppression. (aacrjournals.org)

Efficacy

Head and neck squamous cell carcinoma (R/M, first‑line; ficerafusp alfa + pembrolizumab) - ASCO 2023 interim expansion cohort (stage 1; CPS ≥1; n=18 evaluable): ORR 44% overall; 58% in HPV‑negative subgroup; acneiform rash common; no treatment‑related deaths. (ascopubs.org) - Updated 2025 oral presentation (CPS ≥1; HPV‑negative efficacy subset n=28): ORR 54% confirmed (64% including 3 unconfirmed); CR 21%; median PFS 9.9 months; median DOR 21.7 months; median OS 21.3 months; 2‑year OS 46%. (Company report of ASCO 2025 dataset; pivotal FORTIFI‑HN01 subsequently initiated.) (ir.bicara.com)

Squamous cell carcinoma of the anal canal (post‑chemotherapy; ficerafusp alfa + pembrolizumab) - ASCO GI 2025 phase 1/1b dose‑expansion: among 22 evaluable patients, ORR 32% (95% CI 13.9–54.9), disease control rate 64%; 12‑month PFS rate 36%. (ascopubs.org)

Note: Results above are from early‑phase, single‑arm cohorts and should be interpreted cautiously until randomized data are available (e.g., FORTIFI‑HN01). (ir.bicara.com)

Safety

Across early studies, the combination with pembrolizumab showed a tolerable profile with class‑consistent toxicities: - Most common treatment‑related adverse events (all grades): acneiform rash (≈50–76%), fatigue (≈43%), hypophosphatemia (≈38%), epistaxis/pruritus in SCAC. Grade ≥3 TRAEs included anemia (~19% in SCAC cohort) and acneiform rash (~12%). Discontinuations for TRAEs were infrequent (≤8% reported). (ascopubs.org)

Further reading

• Cancer Research (peer‑reviewed): BCA101 is a tumor‑targeted bifunctional fusion antibody that simultaneously inhibits EGFR and TGF‑β signaling to durably suppress tumor growth. (aacrjournals.org)
• ASCO 2023 abstract (HNSCC, 1L): Dose expansion results of BCA101 with pembrolizumab. (ascopubs.org)
• ASCO GI 2025 abstract (SCAC): Ficerafusp alfa + pembrolizumab preliminary expansion results. (ascopubs.org)
• Pivotal trial information (FORTIFI‑HN01, Phase 2/3, 1L R/M HNSCC). (clinicaltrials.ucbraid.org)
• Company communications summarizing ASCO 2025 HNSCC updates (efficacy and survival metrics). (ir.bicara.com)

ClinicalTrials registration for the ongoing Phase 1/1b program: NCT04429542 (monotherapy and combinations, including HNSCC and SCAC cohorts). (clinicaltrials.ucsd.edu)

Last updated: Oct 2025