Trial: FORTIFI-HN01: A Study of Ficerafusp Alf…

Trial Details

Sponsor: Bicara Therapeutics (industry)

Phase: 2/3

Start date: Jan. 28, 2025

Planned enrollment: 650

Trial ID: NCT06788990

More trial details at ClinicalTrials.gov

Show Summary from Sponsor

Investigational Drug AI Analysis

Show for: Ficerafusp alfa (BCA101, FMAB2)

Overview

Ficerafusp alfa (BCA101; FMAB2) is an investigational intravenous cancer therapy studied alone and with pembrolizumab. Human results are available, but the reported efficacy findings are preliminary and come from early-phase, single-arm cohorts rather than a randomized comparison. (pmc.ncbi.nlm.nih.gov)

Mechanism of action

Ficerafusp alfa combines an antibody against EGFR with a portion of the TGF-β receptor that acts as a TGF-β “trap.” The design aims to inhibit EGFR signaling while neutralizing TGF-β in the tumor environment. In a phase I study, weekly doses of at least 500 mg produced prolonged neutralization of TGF-β1 in plasma. (pubmed.ncbi.nlm.nih.gov)

Efficacy

In a first-line phase I/Ib cohort for PD-L1–positive recurrent or metastatic head and neck squamous cell carcinoma, 42 patients received ficerafusp alfa 1,500 mg weekly plus pembrolizumab; 39 were evaluable for response. The confirmed response rate was 54% (15/28) in patients with HPV-negative tumors, including 21% complete responses, and 27% (3/11) in those with HPV-positive tumors. In the HPV-negative group, median response duration was 21.7 months and median progression-free survival was 9.9 months. (ascopubs.org)

A separate conference abstract reported a 57% response rate (17/30 evaluable patients) with a lower, 750-mg weekly dose plus pembrolizumab in HPV-negative disease. In an earlier dose-escalation study across advanced solid tumors, responses occurred in 1/42 evaluable patients receiving ficerafusp alfa alone and 4/13 receiving it with pembrolizumab. These cohorts do not establish how much benefit ficerafusp alfa adds to pembrolizumab. (annalsofoncology.org)

Safety

In the 1,500-mg head-and-neck cohort, 19/42 patients (45%) had a grade 3 treatment-related adverse event and one (2%) had a grade 4 event; none was fatal. The most common grade 3 or higher events were anemia (14%) and acneiform dermatitis (12%). Treatment-related events led to discontinuation of ficerafusp alfa in 5/42 patients (12%). (ascopubs.org)

TrialFetch AI Analysis

Goal: Determine whether adding ficerafusp alfa to first-line pembrolizumab improves outcomes in PD-L1–positive recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), while selecting an optimal biologic dose and evaluating safety.

Patients: Adults with measurable recurrent or metastatic HNSCC arising in the oral cavity, hypopharynx, larynx, or HPV-negative oropharynx; PD-L1 combined positive score ≥1; ECOG performance status 0–1; and no prior systemic therapy for recurrent or metastatic disease. Patients must provide archival tumor tissue or undergo a screening biopsy if tissue is inadequate. Key exclusions include disease amenable to curative local therapy, active CNS metastases, and recent checkpoint inhibitor treatment.

Design: Multicenter, randomized, double-blind, placebo-controlled study. In phase 2, patients are assigned 1:1:1 to two ficerafusp alfa doses or placebo, each with pembrolizumab, to select an optimal biologic dose. In phase 3, patients are assigned 2:1 to the selected dose or placebo, each with pembrolizumab.

Treatments: Ficerafusp alfa is given intravenously at 750 or 1,500 mg weekly in phase 2, then at the selected dose in phase 3; controls receive weekly placebo. All groups receive pembrolizumab 200 mg every 3 weeks, a PD-1 inhibitor used as first-line therapy for PD-L1–positive recurrent or metastatic HNSCC. Ficerafusp alfa combines EGFR blockade with a TGF-β receptor component that traps TGF-β. Preliminary, nonrandomized first-line data showed a 54% confirmed response rate among 28 evaluable patients with HPV-negative disease receiving 1,500 mg weekly plus pembrolizumab; these data do not establish benefit over pembrolizumab alone.

Outcomes: Phase 2 primary measures are treatment-emergent adverse events and blinded independent central review of objective response rate by RECIST 1.1. Phase 3 primary measures are centrally reviewed objective response rate and overall survival. Secondary measures include progression-free survival, duration of response, clinical benefit, safety, and patient-reported deterioration in quality of life and pain.

Burden on patient: Moderate to high. Weekly intravenous study-drug or placebo visits, alongside pembrolizumab every 3 weeks, create substantially more travel and infusion time than pembrolizumab alone. Patients also undergo screening tissue assessment, with a biopsy if archival tissue is unavailable or insufficient, plus imaging, safety monitoring, and quality-of-life questionnaires. Phase 2 dose selection incorporates pharmacokinetic and pharmacodynamic data, which may require additional sampling; the schedule is not specified.

Last updated: Sep 2026

Eligibility

Caution: ClinicalTrials.gov appears to have newer eligibility criteria than the version saved here. Review the current criteria in ClinicalTrials.gov.

Show Criteria

Inclusion Criteria:

* Age ≥18 years on the day the Informed Consent Form is signed.

* Histologically or cytologically confirmed R or M HNSCC. Eligible primary tumor locations are oral cavity, hypopharynx, larynx or oropharynx (with documented HPV-negative disease if presenting with OPSCC). Note: primary tumor location of paranasal sinuses and nasopharynx, any histology are excluded.

* No prior systemic therapy administered in the R or M setting; and completed systemic therapy \>6 months prior if given as part of multimodal treatment for locoregionally advanced disease in the adjuvant or definitive setting.

* Archival tumor tissue or willing to undergo pretreatment biopsy at Screening if archival tissue is insufficient or unavailable.

* PD-L1 CPS ≥1 (by PD-L1 IHC 22C3 pharmDx assay).

* Measurable disease based on RECIST 1.1.

* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

* Adequate organ function, as defined in the protocol.

Exclusion Criteria:

* Disease suitable for local therapy administered with curative intent.

* Prior treatment with anti-TGFβ therapy.

* Prior therapy with an anti-EGFR antibody (exception: radio sensitizing agents and multimodal treatment for locoregionally advanced disease).

* Prior history of Grade ≥2 intolerance or hypersensitivity reaction to anti-EGFR therapy or other murine proteins.

* Prior therapy with an immune checkpoint inhibitor completed within 6 months prior to study treatment initiation.

* Progressive disease \<6 months from completion of curative intent systemic therapy for locoregionally advanced HNSCC.

* Life expectancy less than 3 months.

* Known active central nervous system metastases, history of spinal cord compression from tumor involvement, a history of carcinomatous meningitis, or leptomeningeal disease are excluded.

* Current active major bleeding, or a recent major bleeding episode within 4 weeks prior to enrollment.

* Subject participated in another clinical study or received treatment with another investigational drug must wait at least 5 half-lives of the treatment received or 4 weeks (whichever is shorter) following prior therapy.

* Active autoimmune disease requiring systemic treatment in the past 2 years.

* Subjects with chronic hepatitis B virus (HBV) infection with active disease who meet the criteria for anti-HBV therapy and are not on a suppressive antiviral therapy prior to initiation of study treatment.

* Subjects with a known history of hepatitis C virus (HCV) who have not completed curative antiviral treatment or have an HCV viral load above the limit of quantification at Screening.

* Known history of human immunodeficiency virus (HIV).

* Receipt of any organ transplantation, including autologous and allogeneic stem cell transplantation, with the exception of transplants that do not require immunosuppression.

* Known to be diagnosed and/or treated for any other additional malignancy within 2 years prior to randomization with the exception of the following: curatively treated basal cell carcinoma or squamous cell carcinoma of the skin, and curatively resected in situ cervical cancer, and curatively resected in situ breast cancer, and low-risk early stage prostate cancer.

* Any condition requiring systemic treatment with either corticosteroids (\>10 mg daily of prednisone or equivalent) or other immunosuppressive medication within 7 days prior to the first dose of study treatment, except for topical, intranasal, intrabronchial, or ocular steroids.

* Use of a live or live attenuated vaccine within 4 weeks prior to Screening.

Other Inclusion/Exclusion criteria may apply as defined in the protocol.

Sites (129)

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Site #0306

Kingswood, New South Wales, 2747, Australia

A Multicenter, Randomized, Double-blind, Phase 2/3 Study of Ficerafusp Alfa (BCA101) or Placebo in Combination With Pembrolizumab for First-Line Treatment of PD-L1-positive, Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

Trial Details

Show Summary from Sponsor

More details:

Investigational Drug AI Analysis

Show for: Ficerafusp alfa (BCA101, FMAB2)

Overview

Mechanism of action

Efficacy

Safety

Further reading

TrialFetch AI Analysis

Eligibility

Show Criteria

Sites (129)

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