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)

May 29, 2026 updated by: Bicara Therapeutics

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

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).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Estimated)

650

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Argentina
      • Buenos Aires, Argentina, C1190
      • Buenos Aires, Argentina, C1425
      • Rosario, Argentina, CP2000
      • Santa Fe, Argentina, S2002KDT
  • Australia
    • New South Wales
      • Camperdown, New South Wales, Australia, 2050
      • Kingswood, New South Wales, Australia, 2747
      • Waratah, New South Wales, Australia, 2298
    • Queensland
      • Southport, Queensland, Australia, 4215
      • Tugun, Queensland, Australia, 4224
    • Victoria
      • Heidelberg, Victoria, Australia, 3084
      • North Melbourne, Victoria, Australia, 3051
    • Western Australia
      • Murdoch, Western Australia, Australia, 6150
  • Austria
      • Salzburg, Austria, 5020
      • Vienna, Austria, 1090
  • Belgium
  • Brazil
      • Santa Cruz do Sul, Brazil, 96835-100
      • São José do Rio Preto, Brazil, 15090-000
  • Canada
      • Toronto, Canada, M4N 3M5
    • British Columbia
      • Vancouver, British Columbia, Canada, V5Z 4E6
    • Quebec
      • Montreal, Quebec, Canada, H2X 0C1
  • Czechia
      • Hradec Králové, Czechia, 500 03
      • Prague, Czechia, 15006
  • France
      • Amiens, France, 80480
      • Bordeaux, France, 33075
      • Lille, France, 59000
      • Lyon, France, 69004
      • Paris, France, 75005
      • Rennes, France, 35042
      • Saint-Grégoire, France, 35760
      • Strasbourg, France, 67200
      • Toulouse, France, 31059
      • Vandœuvre-lès-Nancy, France, 54519
      • Villejuif, France, 94805
  • Germany
      • Aachen, Germany, 52074
      • Berlin, Germany, 12200
      • Berlin, Germany, 12351
      • Braunschweig, Germany, 38114
      • Chemnitz, Germany, 09116
      • Dresden, Germany, 01067
      • Düsseldorf, Germany, 40225
      • Hanover, Germany, 30625
      • Karlsruhe, Germany, 76137
      • München, Germany, 81675
      • Stuttgart, Germany, 70174
      • Ulm, Germany, 89075
  • Greece
      • Athens, Greece, 12461
      • Larissa, Greece, 41110
  • Ireland
      • Cork, Ireland, T12 DC4A
      • Dublin, Ireland, D08 NHY1
      • Dublin, Ireland, D09 V2N0
  • Italy
  • Malaysia
      • George Town, Malaysia, 11200
      • Kuala Lumpur, Malaysia, 50586
      • Kuching, Malaysia, 93200
  • New Zealand
      • Christchurch, New Zealand, 8011
      • Rotorua, New Zealand, 3010
  • Poland
      • Gdansk, Poland, 80-214
      • Gliwice, Poland, 44-102
      • Katowice, Poland, 40-519
      • Konin, Poland, 62-500
      • Krakow, Poland, 31-826
      • Siedlce, Poland, 08-110
      • Warsaw, Poland, 02-781
  • Portugal
      • Braga, Portugal, 4710-243
      • Coimbra, Portugal
      • Lisbon, Portugal, 1099-023
      • Portimão, Portugal, 8500-338
      • Porto, Portugal, 4200-072
      • Porto, Portugal, 4200-319
      • Senhora da Hora, Portugal, 4464-509
      • Vila Nova de Gaia, Portugal, 4434-502
  • Singapore
      • Singapore, Singapore, 168583
  • South Korea
      • Hwasun, South Korea, 58128
      • Seongnam, South Korea, 13620
      • Seoul, South Korea, 3080
  • Spain
      • Barcelona, Spain, 08035
      • Barcelona, Spain, 08036
      • Barcelona, Spain, 08041
      • Barcelona, Spain, 08908
      • Madrid, Spain, 28027
      • Madrid, Spain, 28041
      • Pamplona, Spain, 31008
      • Santander, Spain, 39008
      • Valencia, Spain, 46010
      • Valencia, Spain, 46014
  • Switzerland
      • Geneva, Switzerland, 1205
  • Taiwan
      • Taipei, Taiwan, 10002
  • United Kingdom
      • Aberdeen, United Kingdom, AB25 2ZN
      • Birmingham, United Kingdom, B15 2TH
      • Cambridge, United Kingdom, CB2 0QQ
      • Glasgow, United Kingdom, G12 0YN
      • Leeds, United Kingdom, LS9 7TF
      • Liverpool, United Kingdom, L7 8YA
      • London, United Kingdom, SW3 6JJ
      • London, United Kingdom, WC1E 6AG
      • Manchester, United Kingdom, M20 4BX
      • Middlesex, United Kingdom, HA6 2RN
      • Nottingham, United Kingdom, NG5 1PB
      • Oxford, United Kingdom, OX3 7LE
      • Portsmouth, United Kingdom, PO6 3LY
      • Sutton, United Kingdom, SM2 5PT
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
    • Arizona
      • Phoenix, Arizona, United States, 85054
    • California
      • La Jolla, California, United States, 92093
      • Los Angeles, California, United States, 90095
      • Sacramento, California, United States, 95817
      • San Francisco, California, United States, 94143
      • Stanford, California, United States, 94305
    • Colorado
      • Aurora, Colorado, United States, 80012
      • Aurora, Colorado, United States, 80045
      • Aurora, Colorado, United States, 80045
    • Delaware
      • Newark, Delaware, United States, 19713
    • Florida
      • Jacksonville, Florida, United States, 32224
      • Palm Bay, Florida, United States, 32901
      • Tampa, Florida, United States, 33612
    • Illinois
      • Chicago, Illinois, United States, 60064
    • Iowa
      • Iowa City, Iowa, United States, 52242
    • Kansas
      • Westwood, Kansas, United States, 66205
    • Kentucky
      • Lexington, Kentucky, United States, 40536
      • Louisville, Kentucky, United States, 40202
      • Louisville, Kentucky, United States, 40202
    • Maryland
      • Baltimore, Maryland, United States, 21201
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
      • Boston, Massachusetts, United States, 02136
    • Minnesota
      • Maplewood, Minnesota, United States, 55109
      • Rochester, Minnesota, United States, 55905
    • Missouri
      • St Louis, Missouri, United States, 63110
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
      • Newark, New Jersey, United States, 07103
    • New York
      • New York, New York, United States, 10021
      • New York, New York, United States, 10003
    • North Carolina
      • Durham, North Carolina, United States, 27703
    • Ohio
      • Canton, Ohio, United States, 44708
      • Cincinnati, Ohio, United States, 45221
      • Cleveland, Ohio, United States, 44195
      • Cleveland, Ohio, United States, 44106
    • Oregon
      • Portland, Oregon, United States, 97213
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15206
      • Pittsburgh, Pennsylvania, United States, 15240
    • Rhode Island
      • Providence, Rhode Island, United States, 02903
    • South Carolina
      • Charleston, South Carolina, United States, 29425
    • Tennessee
      • Nashville, Tennessee, United States, 37203
      • Nashville, Tennessee, United States, 37232
    • Texas
      • Houston, Texas, United States, 77005
      • Waco, Texas, United States, 676712
    • Virginia
      • Charlottesville, Virginia, United States, 22904
      • Richmond, Virginia, United States, 23219
      • Richmond, Virginia, United States, 23249
    • Washington
      • Edmonds, Washington, United States, 98026
      • Seattle, Washington, United States, 98109
      • Seattle, Washington, United States, 98104
      • Vancouver, Washington, United States, 98684
    • Wisconsin
      • Madison, Wisconsin, United States, 53705
      • Madison, Wisconsin, United States, 53792

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.
  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Phase 2 Arm A
ficerafusp alfa 1500 mg QW + pembrolizumab 200 mg every 3 weeks (Q3W)
Drug: Ficerafusp alfa
Investigational
Drug: Pembrolizumab (KEYTRUDA®)
Immunotherapy agent used in combination with investigational agent
Experimental: Phase 2 Arm B
ficerafusp alfa 750 mg QW + pembrolizumab 200 mg Q3W
Drug: Ficerafusp alfa
Investigational
Drug: Pembrolizumab (KEYTRUDA®)
Immunotherapy agent used in combination with investigational agent
Placebo Comparator: Phase 2 Arm C
placebo QW + pembrolizumab 200 mg Q3W
Drug: Placebo
Placebo Control
Drug: Pembrolizumab (KEYTRUDA®)
Immunotherapy agent used in combination with investigational agent
Experimental: Phase 3 OBD Arm
ficerafusp alfa OBD + pembrolizumab 200 mg Q3W
Drug: Ficerafusp alfa
Investigational
Drug: Pembrolizumab (KEYTRUDA®)
Immunotherapy agent used in combination with investigational agent
Placebo Comparator: Phase 3 Arm C
placebo QW + pembrolizumab 200 mg Q3W
Drug: Placebo
Placebo Control
Drug: Pembrolizumab (KEYTRUDA®)
Immunotherapy agent used in combination with investigational agent

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase 2 - Incidence and severity of TEAEs, treatment-treatment emergent SAEs TEAEs leading to dose interruption, dose reduction, or permanent discontinuation.
Time Frame: Up to 30 days post end of treatment for TEAEs (90 days for SAEs).
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)
Time Frame: Approximately 1 year.
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.
Time Frame: Approximately 2 years.
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)
Time Frame: Approximately 3 years.
OS: Defined as the time from the randomization to death due to any cause.
Approximately 3 years.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase 2 - Duration of Response (DOR) per RECIST 1.1 by BICR.
Time Frame: Approximately 1 year.
DOR: For subjects who demonstrated CR or PR, DOR is defined as the time from first documented evidence of CR or PR until disease progression or death, whichever occurs first, 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.
Time Frame: Up to 30 days post end of treatment for TEAEs (90 days for SAEs).
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 3 - Progression-free survival (PFS) per RECIST 1.1 by BICR.
Time Frame: Approximately 3 years.
PFS: Defined as the time from randomization to the first documented PD per RECIST 1.1 as determined by BICR or death due to any cause, whichever occurs first.
Approximately 3 years.
Phase 3 - Objective Response Rate (ORR) per RECIST 1.1 by BICR.
Time Frame: Approximately 3 years.
ORR: Defined as confirmed CR + PR per RECIST 1.1 by BICR. (FAS).
Approximately 3 years.
Phase 3 - Duration of Response (DOR) per RECIST 1.1 by BICR.
Time Frame: Approximately 3 years.
DOR: For subjects who demonstrated CR or PR, DOR is defined as the time from first documented evidence of CR or PR until disease progression or death, whichever occurs first per RECIST 1.1 by BICR.
Approximately 3 years.
Phase 3 - Clinical Benefit Rate (CBR) per RECIST 1.1 by BICR.
Time Frame: Approximately 3 years.
Clinical Benefit Rate: For subject who demonstrated CR + PR + SD>6 months per RECIST 1.1 by BICR.
Approximately 3 years.
Phase 3 - ORR, per RECIST 1.1 by investigator's assessment.
Time Frame: Approximately 3 years.
ORR, per RECIST 1.1 as determined by investigator's assessment.
Approximately 3 years.
Phase 3 - DOR, per RECIST 1.1 by investigator's assessment.
Time Frame: Approximately 3 years.
DOR, per RECIST 1.1 as determined by investigator's assessment.
Approximately 3 years.
Phase 3 - PFS, per RECIST 1.1 by investigator's assessment.
Time Frame: Approximately 3 years.
PFS, per RECIST 1.1 as determined by investigator's assessment.
Approximately 3 years.
Phase 3 - 14. Time to deterioration (TTD) in global health status measured by the EORTC QLQ C30 items for global health status and quality of life scale (item 29/30)
Time Frame: Approximately 3 years.

To evaluate TTD in global health status/quality of life in subjects treated with ficerafusp alfa in combination with pembrolizumab versus placebo plus pembrolizumab.

TTD is defined as the time from Baseline to the first onset of a ≥10-point negative change (decrease) from Baseline in QoL using the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30 Item 30) score. Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher value indicates a better level of function.
Approximately 3 years.
Phase 3 - Time to deterioration (TTD) in pain measured by the EORTC HN 35 (items 31-34) pain domain.
Time Frame: Approximately 3 years.

To evaluate TTD in pain in subjects treated with ficerafusp alfa in combination with pembrolizumab versus placebo plus pembrolizumab.

TTD defined as the time from first dose (baseline) to change in pain score by 10-point from baseline, using the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core Head and Neck Module (EORTC HN35). A higher score indicates a higher level of symptom burden.
Approximately 3 years.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Bicara Therapeutics

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 28, 2025

Primary Completion (Estimated)

April 1, 2028

Study Completion (Estimated)

July 1, 2029

Study Registration Dates

First Submitted

January 10, 2025

First Submitted That Met QC Criteria

January 17, 2025

First Posted (Actual)

January 23, 2025

Study Record Updates

Last Update Posted (Actual)

June 2, 2026

Last Update Submitted That Met QC Criteria

May 29, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BCA101X301
  • 2024-519654-37-00 (Ctis)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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