FORTIFI-HN01: A Study of Ficerafusp Alfa (BCA101) or Placebo in Combination With Pembrolizumab in First-Line PD-L1-pos, R or M HNSCC

NCT ID: NCT06788990

Last Updated: 2025-11-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2/PHASE3

Total Enrollment

650 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-01-28

Study Completion Date

2029-07-31

Brief Summary

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Ficerafusp alfa is directed against two targets, Epidermal Growth Factor Receptor (EGFR) and Transforming Growth Factor beta (TGF-β).

This study intends to evaluate the safety and efficacy of ficerafusp alfa in combination with pembrolizumab versus placebo with pembrolizumab in 1L PD-L1-positive, recurrent or metastatic Head and Neck Squamous Cell Carcinoma (HNSCC).

Detailed Description

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The mechanism of action of ficerafusp alfa involves dual targeting of two cancer targets, EGFR and TGF-β, which are known to drive solid tumor growth and metastasis.

Phase 2 of the study will identify an optimal biologic dose (OBD) supported by the safety, tolerability, PK, PD, and efficacy data of ficerafusp alfa. In this part, eligible subjects will be randomized to one of three treatment arms at a 1:1:1 ratio:

* Arm A: ficerafusp alfa 1500 mg once weekly (QW) + pembrolizumab 200 mg every three weeks (Q3W).
* Arm B: ficerafusp alfa 750 mg QW + pembrolizumab 200 mg Q3W.
* Arm C (control): placebo QW + pembrolizumab 200 mg Q3W.

The primary objective for the phase 3 portion is to compare the efficacy in subjects treated with ficerafusp alfa at the selected OBD in combination with pembrolizumab versus placebo with pembrolizumab. Eligible subjects will be randomized 2:1 in the treatment versus control arm during the phase 3 portion.

Conditions

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Metastatic Head and Neck Squamous Cell Carcinoma Recurrent Head and Neck Squamous Cell Carcinoma

Keywords

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Phase 2/3 Ficerafusp alfa BCA101 Recurrent Head and Neck Squamous Cell Carcinoma (R HNSCC) Metastatic Head and Neck Squamous Cell Carcinoma (M HNSCC) Pembrolizumab EGFR TGF-beta

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Randomized
Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Phase 2 Arm A

ficerafusp alfa 1500 mg QW + pembrolizumab 200 mg every 3 weeks (Q3W)

Group Type EXPERIMENTAL

Ficerafusp alfa

Intervention Type DRUG

Investigational

Pembrolizumab (KEYTRUDA®)

Intervention Type DRUG

Immunotherapy agent used in combination with investigational agent

Phase 2 Arm B

ficerafusp alfa 750 mg QW + pembrolizumab 200 mg Q3W

Group Type EXPERIMENTAL

Ficerafusp alfa

Intervention Type DRUG

Investigational

Pembrolizumab (KEYTRUDA®)

Intervention Type DRUG

Immunotherapy agent used in combination with investigational agent

Phase 2 Arm C

placebo QW + pembrolizumab 200 mg Q3W

Group Type PLACEBO_COMPARATOR

Pembrolizumab (KEYTRUDA®)

Intervention Type DRUG

Immunotherapy agent used in combination with investigational agent

Placebo

Intervention Type DRUG

Placebo Control

Phase 3 OBD Arm

ficerafusp alfa OBD + pembrolizumab 200 mg Q3W

Group Type EXPERIMENTAL

Ficerafusp alfa

Intervention Type DRUG

Investigational

Pembrolizumab (KEYTRUDA®)

Intervention Type DRUG

Immunotherapy agent used in combination with investigational agent

Phase 3 Arm C

placebo QW + pembrolizumab 200 mg Q3W

Group Type PLACEBO_COMPARATOR

Pembrolizumab (KEYTRUDA®)

Intervention Type DRUG

Immunotherapy agent used in combination with investigational agent

Placebo

Intervention Type DRUG

Placebo Control

Interventions

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Ficerafusp alfa

Investigational

Intervention Type DRUG

Pembrolizumab (KEYTRUDA®)

Immunotherapy agent used in combination with investigational agent

Intervention Type DRUG

Placebo

Placebo Control

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Bicara Therapeutics

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Site # 0137

Birmingham, Alabama, United States

Site Status RECRUITING

Site #0147

Phoenix, Arizona, United States

Site Status RECRUITING

Site #0107

La Jolla, California, United States

Site Status RECRUITING

Site #0106

Los Angeles, California, United States

Site Status RECRUITING

Site#0144

Sacramento, California, United States

Site Status RECRUITING

Site #0150

Stanford, California, United States

Site Status RECRUITING

Site #0122

Aurora, Colorado, United States

Site Status RECRUITING

Site #0124

Aurora, Colorado, United States

Site Status RECRUITING

Site#0121

Aurora, Colorado, United States

Site Status RECRUITING

Site#0127

Newark, Delaware, United States

Site Status RECRUITING

Site #0148

Jacksonville, Florida, United States

Site Status RECRUITING

Site #0136

Palm Bay, Florida, United States

Site Status RECRUITING

Site #0105

Tampa, Florida, United States

Site Status RECRUITING

Site #0133

Chicago, Illinois, United States

Site Status RECRUITING

Site#0140

Iowa City, Iowa, United States

Site Status RECRUITING

Site #0149

Westwood, Kansas, United States

Site Status RECRUITING

Site#0109

Lexington, Kentucky, United States

Site Status RECRUITING

Site#0111

Louisville, Kentucky, United States

Site Status RECRUITING

Site#0115

Louisville, Kentucky, United States

Site Status RECRUITING

Site #0112

Baltimore, Maryland, United States

Site Status RECRUITING

Site #0131

Boston, Massachusetts, United States

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Site#0101

Boston, Massachusetts, United States

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Site #0146

Rochester, Minnesota, United States

Site Status RECRUITING

Site #0119

Hackensack, New Jersey, United States

Site Status RECRUITING

Site#0142

New York, New York, United States

Site Status RECRUITING

Site#0118

Durham, North Carolina, United States

Site Status RECRUITING

Site#0154

Canton, Ohio, United States

Site Status RECRUITING

Site#0117

Cincinnati, Ohio, United States

Site Status RECRUITING

Site #0151

Cleveland, Ohio, United States

Site Status RECRUITING

Site #0108

Cleveland, Ohio, United States

Site Status RECRUITING

Site #0113

Portland, Oregon, United States

Site Status RECRUITING

Site #0103

Pittsburgh, Pennsylvania, United States

Site Status RECRUITING

Site #0123

Pittsburgh, Pennsylvania, United States

Site Status RECRUITING

Site #0132

Providence, Rhode Island, United States

Site Status RECRUITING

Site#0104

Charleston, South Carolina, United States

Site Status RECRUITING

Site#0126

Nashville, Tennessee, United States

Site Status RECRUITING

Site #0116

Nashville, Tennessee, United States

Site Status RECRUITING

Site#0102

Houston, Texas, United States

Site Status RECRUITING

Site#0134

Charlottesville, Virginia, United States

Site Status RECRUITING

Site #0129

Richmond, Virginia, United States

Site Status RECRUITING

Site #0125

Seattle, Washington, United States

Site Status RECRUITING

Site#0120

Vancouver, Washington, United States

Site Status RECRUITING

Site #0141

Madison, Wisconsin, United States

Site Status RECRUITING

Site#0302

Camperdown, New South Wales, Australia

Site Status RECRUITING

Site #0306

Kingswood, New South Wales, Australia

Site Status RECRUITING

Site#0304

Waratah, New South Wales, Australia

Site Status RECRUITING

Site #0305

Southport, Queensland, Australia

Site Status RECRUITING

Site#0307

Tugun, Queensland, Australia

Site Status RECRUITING

Site #0303

Heidelberg, Victoria, Australia

Site Status RECRUITING

Site#0301

North Melbourne, Victoria, Australia

Site Status RECRUITING

Site#0308

Murdoch, Western Australia, Australia

Site Status RECRUITING

Site #0202

Vancouver, British Columbia, Canada

Site Status RECRUITING

Site #0203

Montreal, Quebec, Canada

Site Status RECRUITING

Site #0401

Christchurch, , New Zealand

Site Status RECRUITING

Site#0402

Rotorua, , New Zealand

Site Status RECRUITING

Site #1506

Braga, , Portugal

Site Status RECRUITING

Site #0504

Aberdeen, , United Kingdom

Site Status RECRUITING

Site #0505

London, , United Kingdom

Site Status RECRUITING

Site # 0501

Sutton, , United Kingdom

Site Status RECRUITING

Countries

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United States Australia Canada New Zealand Portugal United Kingdom

Central Contacts

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Medical Affairs

Role: CONTACT

Phone: 1-617-468-4219

Email: [email protected]

Facility Contacts

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Other Identifiers

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2024-519654-37-00

Identifier Type: CTIS

Identifier Source: secondary_id

BCA101X301

Identifier Type: -

Identifier Source: org_study_id