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

NCT06788990 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: BCA101X3012024-519654-37-00
• Study Type: interventional
• Target: 650
• Locations: 14 countries
• Sites: 121

Brief Summary

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).

Conditions

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

Keywords

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; HNSCC; PD-L1+; Head and Neck cancer; Oral Cavity; Oropharynx; Larynx; Hypopharynx

Outcome Measures

Primary Outcomes (4)

• Phase 2 - Incidence and severity of TEAEs, treatment-treatment emergent SAEs TEAEs leading to dose interruption, dose reduction, or permanent discontinuation.

  To assess safety and tolerability of ficerafusp alfa with pembrolizumab.

  Up to 30 days post end of treatment for TEAEs (90 days for SAEs).

• Phase 2 - Objective Response Rate (ORR) per RECIST 1.1 by blinded independent central review (BICR)

  ORR is defined as the proportion of subjects in the DDS who have a confirmed CR or PR per RECIST 1.1. by BICR.

  Approximately 1 year.

• Phase 3 - Objective Response Rate (ORR) per RECIST 1.1 by BICR.

  ORR is defined as the proportion of subjects in the DDS who have a confirmed CR or PR per RECIST 1.1. by BICR.

  Approximately 2 years.

• Phase 3 - Overall Survival (OS)

  OS: Defined as the time from the randomization to death due to any cause.

  Approximately 3 years.

Secondary Outcomes (11)

• Phase 2 - Duration of Response (DOR) per RECIST 1.1 by BICR.

  Approximately 1 year.

• Phase 3 - Incidence and severity of TEAEs, treatment-treatment emergent SAEs TEAEs leading to dose interruption, dose reduction, or permanent discontinuation.

  Up to 30 days post end of treatment for TEAEs (90 days for SAEs).

• Phase 3 - Progression-free survival (PFS) per RECIST 1.1 by BICR.

  Approximately 3 years.

• Phase 3 - Objective Response Rate (ORR) per RECIST 1.1 by BICR.

  Approximately 3 years.

• Phase 3 - Duration of Response (DOR) per RECIST 1.1 by BICR.

  Approximately 3 years.

Study Arms (5)

Phase 2 Arm A

EXPERIMENTAL

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

Drug: Ficerafusp alfa; Drug: Pembrolizumab (KEYTRUDA®)

Phase 2 Arm B

EXPERIMENTAL

ficerafusp alfa 750 mg QW + pembrolizumab 200 mg Q3W

Drug: Ficerafusp alfa; Drug: Pembrolizumab (KEYTRUDA®)

Phase 2 Arm C

PLACEBO COMPARATOR

placebo QW + pembrolizumab 200 mg Q3W

Drug: Pembrolizumab (KEYTRUDA®); Drug: Placebo

Phase 3 OBD Arm

EXPERIMENTAL

ficerafusp alfa OBD + pembrolizumab 200 mg Q3W

Drug: Ficerafusp alfa; Drug: Pembrolizumab (KEYTRUDA®)

Phase 3 Arm C

PLACEBO COMPARATOR

placebo QW + pembrolizumab 200 mg Q3W

Drug: Pembrolizumab (KEYTRUDA®); Drug: Placebo

Interventions

Ficerafusp alfa DRUG

Investigational

Phase 2 Arm A; Phase 2 Arm B; Phase 3 OBD Arm

Pembrolizumab (KEYTRUDA®) DRUG

Immunotherapy agent used in combination with investigational agent

Phase 2 Arm A; Phase 2 Arm B; Phase 2 Arm C; Phase 3 Arm C; Phase 3 OBD Arm

Placebo DRUG

Placebo Control

Phase 2 Arm C; Phase 3 Arm C

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Bicara Therapeutics: lead

Study Sites (129)

Site # 0137

Birmingham, Alabama, 35233, United States

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Site #0147

Phoenix, Arizona, 85054, United States

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Site #0107

La Jolla, California, 92093, United States

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Site #0106

Los Angeles, California, 90095, United States

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Site#0144

Sacramento, California, 95817, United States

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Site #0130

San Francisco, California, 94143, United States

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Site #0150

Stanford, California, 94305, United States

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Site #0122

Aurora, Colorado, 80012, United States

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Site #0124

Aurora, Colorado, 80045, United States

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Site#0121

Aurora, Colorado, 80045, United States

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Site#0127

Newark, Delaware, 19713, United States

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Site #0148

Jacksonville, Florida, 32224, United States

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Site #0136

Palm Bay, Florida, 32901, United States

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Site #0105

Tampa, Florida, 33612, United States

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Site #0133

Chicago, Illinois, 60064, United States

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Site#0140

Iowa City, Iowa, 52242, United States

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Site #0149

Westwood, Kansas, 66205, United States

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Site#0109

Lexington, Kentucky, 40536, United States

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Site#0111

Louisville, Kentucky, 40202, United States

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Site#0115

Louisville, Kentucky, 40202, United States

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Site #0112

Baltimore, Maryland, 21201, United States

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Site #0131

Boston, Massachusetts, 02114, United States

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Site#0101

Boston, Massachusetts, 02136, United States

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Site #0156

Maplewood, Minnesota, 55109, United States

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Site #0146

Rochester, Minnesota, 55905, United States

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Site #0114

St Louis, Missouri, 63110, United States

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Site #0119

Hackensack, New Jersey, 07601, United States

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Site #0145

Newark, New Jersey, 07103, United States

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Site #0155

New York, New York, 10003, United States

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Site#0142

New York, New York, 10021, United States

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Site#0118

Durham, North Carolina, 27703, United States

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Site#0154

Canton, Ohio, 44708, United States

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Site#0117

Cincinnati, Ohio, 45221, United States

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Site #0151

Cleveland, Ohio, 44106, United States

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Site #0108

Cleveland, Ohio, 44195, United States

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Site #0113

Portland, Oregon, 97213, United States

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Site #0103

Pittsburgh, Pennsylvania, 15206, United States

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Site #0123

Pittsburgh, Pennsylvania, 15240, United States

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Site #0132

Providence, Rhode Island, 02903, United States

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Site#0104

Charleston, South Carolina, 29425, United States

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Site#0126

Nashville, Tennessee, 37203, United States

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Site #0116

Nashville, Tennessee, 37232, United States

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Site#0102

Houston, Texas, 77005, United States

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Site #0152

Waco, Texas, 676712, United States

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Site#0134

Charlottesville, Virginia, 22904, United States

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Site #0129

Richmond, Virginia, 23219, United States

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Site #0138

Richmond, Virginia, 23249, United States

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Site #0125

Seattle, Washington, 98109, United States

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Site#0120

Vancouver, Washington, 98684, United States

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Site #0141

Madison, Wisconsin, 53705, United States

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Site #0157

Madison, Wisconsin, 53792, United States

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Site#0302

Camperdown, New South Wales, 2050, Australia

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Site #0306

Kingswood, New South Wales, 2747, Australia

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Site#0304

Waratah, New South Wales, 2298, Australia

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Site #0305

Southport, Queensland, 4215, Australia

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Site#0307

Tugun, Queensland, 4224, Australia

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Site #0303

Heidelberg, Victoria, 3084, Australia

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Site#0301

North Melbourne, Victoria, 3051, Australia

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Site#0308

Murdoch, Western Australia, 6150, Australia

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Site #1602

Salzburg, 5020, Austria

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Site #1601

Vienna, 1090, Austria

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Site #1007

Bruges, 8000, Belgium

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Site #1005

Mons, 7000, Belgium

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Site #1002

Namur, 5000, Belgium

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Site #1003

Namur, 5530, Belgium

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Site #1001

Sint-Niklaas, 9100, Belgium

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Site #1006

Wilrijk, 2610, Belgium

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Site #0202

Vancouver, British Columbia, V5Z 4E6, Canada

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Site #0203

Montreal, Quebec, H2X 0C1, Canada

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Site #2102

Prague, 15006, Czechia

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Site #0809

Amiens, 80480, France

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Site #0810

Lyon, 69004, France

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Site #0805

Rennes, 35042, France

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Site #0807

Saint-Grégoire, 35760, France

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Site #0808

Strasbourg, 67200, France

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Site #0806

Vandœuvre-lès-Nancy, 54519, France

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Site #0801

Villejuif, 94805, France

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Site #0710

Aachen, 52074, Germany

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Site #0707

Dresden, 01067, Germany

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Site #0706

Düsseldorf, 40225, Germany

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Site #0717

Karlsruhe, 76137, Germany

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Site #0602

Dublin, D08 NHY1, Ireland

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Site #0601

Dublin, D09 V2N0, Ireland

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Site #0904

Bologna, 40138, Italy

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Site #0911

Florence, 50134, Italy

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Site #0907

Milan, 20132, Italy

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Site #0901

Milan, 20133, Italy

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Site #0905

Milan, 20142, Italy

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Site #0915

Naples, 80131, Italy

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Site #0908

Palermo, 90127, Italy

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Site #0917

Rome, 00161, Italy

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Site #0918

Rome, 00168, Italy

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Site #0906

Rome, 00186, Italy

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Site #0401

Christchurch, 8011, New Zealand

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Site#0402

Rotorua, 3010, New Zealand

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Site #1401

Gdansk, 80-214, Poland

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Site #1403

Katowice, 40-519, Poland

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Site #1407

Konin, 62-500, Poland

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Site #1404

Krakow, 31-826, Poland

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Site #1402

Siedlce, 08-110, Poland

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Site #1406

Warsaw, 02-781, Poland

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Site #1506

Braga, 4710-243, Portugal

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Site #1503

Coimbra, Portugal

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Site #1508

Lisbon, 1099-023, Portugal

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Site #1501

Portimão, 8500-338, Portugal

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Site #1505

Porto, 4200-072, Portugal

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Site #1507

Porto, 4200-319, Portugal

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Site #1502

Senhora da Hora, 4464-509, Portugal

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Site #1301

Barcelona, 08035, Spain

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Site #1305

Barcelona, 08036, Spain

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Site #1304

Barcelona, 08041, Spain

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Site #1310

Madrid, 28027, Spain

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Site #1303

Madrid, 28041, Spain

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Site #1306

Pamplona, 31008, Spain

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Site #1309

Santander, 39008, Spain

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Site #1307

Valencia, 46010, Spain

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Site #1308

Valencia, 46014, Spain

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Site #0504

Aberdeen, AB25 2ZN, United Kingdom

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Site #0512

Birmingham, B15 2TH, United Kingdom

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Site #0513

Cambridge, CB2 0QQ, United Kingdom

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Site #0511

Leeds, LS9 7TF, United Kingdom

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Site #0507

Liverpool, L7 8YA, United Kingdom

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Site #0505

London, SW3 6JJ, United Kingdom

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Site #0502

London, WC1E 6AG, United Kingdom

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Site #0508

Manchester, M20 4BX, United Kingdom

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Site #0506

Middlesex, HA6 2RN, United Kingdom

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Site #0503

Nottingham, NG5 1PB, United Kingdom

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Site #0515

Oxford, OX3 7LE, United Kingdom

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Site # 0501

Sutton, SM2 5PT, United Kingdom

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MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Camurati-Engelmann Syndrome; Head and Neck Neoplasms; Laryngeal Diseases

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Osteochondrodysplasias; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Respiratory Tract Diseases; Otorhinolaryngologic Diseases

Central Study Contacts

Medical Affairs

CONTACT

1-617-468-4219; FORTIFI_inquiries@bicara.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized

Study Record Dates

• First Submitted: January 10, 2025
• First Posted: January 23, 2025
• Study Start: January 28, 2025
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): July 1, 2029
• Last Updated: March 23, 2026

Record last verified: 2026-03

Locations

ES (9); IT (10); AU (2); GB (12); US (51); FR (7); DE (4); PT (7); IE (2); PL (6); NZ (2); BE (6); CA (2); CZ (1)