Metastatic Head and Neck Squamous Cell CarcinomaPhase 2FORTIFI-FLEXNCT07807163
A Study Evaluating Ficerafusp Alfa (BCA101) QW in Combination With Pembrolizumab vs Alternative Ficerafusp Alfa Dosing in 1L R or M HNSCC
A Phase 2 study testing Ficerafusp alfa and Pembrolizumab (KEYTRUDA®) in people with Metastatic Head and Neck Squamous Cell Carcinoma and Recurrent Head and Neck Squamous Cell Carcinoma, run by Bicara Therapeutics at 7 sites in United States.
Trial summary
Ficerafusp alfa is directed against two targets, Epidermal Growth Factor Receptor (EGFR) and Transforming Growth Factor beta (TGF-β). The study aims to demonstrate that the antitumor activity of an alternative dosing regimen of ficerafusp alfa in combination with pembrolizumab is comparable to the weekly ficerafusp… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Head and Neck Squamous Cell Carcinoma, Recurrent Head and Neck Squamous Cell Carcinoma
- What is being tested?
- Ficerafusp alfa and Pembrolizumab (KEYTRUDA®)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 160 participants
- Where
- 7 sitesUnited States
- Study dates
- Sep 2026to Mar 2029
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
7 sites in 1 country. Contact the study team or a site near you to ask about taking part.
7 sites in 1 country
United States7 sites, 7 recruiting
- Recruiting
Site US069
Baton Rouge, Louisiana, 70809
- Recruiting
Site US077
Fort Myers, Florida, 33980
- Recruiting
Site US078
Orlando, Florida, 32827
- Recruiting
Site US073
Roanoke, Virginia, 24014
- Recruiting
Site US075
St. Petersburg, Florida, 33701
- Recruiting
Site US074
Tyler, Texas, 75702
- Recruiting
Site US076
West Palm Beach, Florida, 33410
About this study
Official title: A Multicenter, Open-label, Randomized Phase 2 Study Evaluating Continuous Weekly Dosing of Ficerafusp Alfa (BCA101) in Combination With Pembrolizumab Versus an Alternative Ficerafusp Alfa Dosing Regimen for First-Line Treatment of 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).
The study aims to demonstrate that the antitumor activity of an alternative dosing regimen of ficerafusp alfa in combination with pembrolizumab is comparable to the weekly ficerafusp alfa regimen in 1L PD-L1-positive, recurrent or metastatic Head and Neck Squamous Cell Carcinoma (HNSCC).
Read the 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.
All participants will receive ficerafusp alfa 1500 mg once weekly (QW in combination with pembrolizumab 200 mg every three weeks (Q3W) for 12 weeks (loading phase). Participants who remain on study without progression at the end of the loading phase will enter the maintenance phase and will be randomized 2:1 to one of the following arms:
Arm A: Ficerafusp alfa 2250 mg Q3W [alternative dose] + pembrolizumab 200 mg Q3W Arm B: Ficerafusp alfa 1500 mg QW [standard dose] + pembrolizumab 200 mg Q3W.
- Conditions
- Metastatic Head and Neck Squamous Cell Carcinoma, Recurrent Head and Neck Squamous Cell Carcinoma
- Being tested
- Ficerafusp alfa, Pembrolizumab (KEYTRUDA®)
- Keywords
- head and neck cancer, HNSCC, recurrent HNSCC, metastatic HNSCC, first line treatment, Phase 2, Recurrent Head and Neck Squamous Cell Carcinoma, Metastatic Head and Neck Squamous Cell Carcinoma, Pembrolizumab, PD-L1+, TGF-beta, oral cavity, oropharynx, larynx, hypopharynx, Ficerafusp alfa, SCCHN, HPVneg, HPV negative, HPV-
- Medical subject headings
- Squamous Cell Carcinoma of Head and Neck, Head and Neck Neoplasms, Camurati-Engelmann Syndrome, Laryngeal Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ficerafusp alfaDrug
investigational agent
Pembrolizumab (KEYTRUDA®)Drug
immunotherapy agent used in combination with investigational agent
| Study group | Role | What they receive |
|---|---|---|
| Arm A | Experimental | Loading phase (12 weeks): Ficerafusp alfa 1500 mg QW (standard dose) + pembrolizumab 200 mg Q3W.
Maintenance phase: Ficerafusp alfa 2250 mg Q3W (alternative dose) + pembrolizumab 200 mg Q3W. Receives: Drug: Ficerafusp alfa; Drug: Pembrolizumab (KEYTRUDA®) |
| Arm B | Experimental | Continuous ficerafusp alfa 1500 mg QW (standard dose) + pembrolizumab 200 mg Q3W. Receives: Drug: Ficerafusp alfa; Drug: Pembrolizumab (KEYTRUDA®) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of participants in maintenance phase who are progression-free as assessed by blinded independent central review (BICR) per RECIST 1.1 and alive.
Measured: Approximately 9 months.
Secondary outcomes (13)
Serum exposure of ficerafusp alfa.
Pre- and post-infusion serum concentrations and area under the curve (AUC) for ficerafusp alfa.
Measured: Approximately 9 months.
Objective response rate (ORR) per RECIST 1.1 by blinded independent central review (BICR).
ORR is defined as the proportion of subjects who have a confirmed CR or PR per RECIST 1.1. by BICR.
Measured: Approximately 1 year.
Disease control rate (DCR) per RECIST 1.1 by blinded independent central review (BICR)
DCR is defined as the proportion of subjects who have a SD, CR or PR per RECIST 1.1. by BICR
Measured: Approximately 1 year.
Clinical Benefit Rate (CBR) per RECIST 1.1 by blinded independent central review (BICR)
CBR is defined as the proportion of subjects who demonstrated CR + PR + SD>6 months per RECIST 1.1 by BICR.
Measured: Approximately 3 years.
Duration of Response (DOR) per RECIST 1.1 by blinded independent central review (BICR).
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.
Measured: Approximately 3 years.
Progression-free survival (PFS) per RECIST 1.1 by blinded independent central review (BICR).
Defined as the time from Cycle 1 Day 1[TK16.1] to the first documented PD per RECIST 1.1 as determined by BICR or death due to any cause, whichever occurs first.
Measured: Approximately 3 years.
Overall Survival (OS)
Defined as the time from the Cycle 1 Day 1 to death due to any cause.
Measured: Approximately 3 years.
Time to Response (TTR) per RECIST 1.1 by blinded independent central review (BICR)
For subjects who demonstrated CR or PR, TTR is defined as the time from Cycle 1 Day 1 to first documented evidence of CR or PR per RECIST 1.1 by BICR.
Measured: Approximately 3 years.
Deep Response Rate by blinded independent central review (BICR)
Defined as the proportion of responders who achieve a deep response.
Measured: Approximately 3 years.
Time to maximum tumor shrinkage
Time to maximum tumor shrinkage is defined as the time from Cycle 1 Day 1 to the maximum reduction in target lesion diameter by BICR.
Measured: Approximately 3 years.
Incidence of ≥Grade 3 TEAEs
Measured: Up to 30 days post end of treatment.
Incidence of Serious adverse events (SAEs)
Measured: Up to 90 days post end of treatment.
Incidence of Adverse events (AEs) leading to dose modifications (dose reduction, interruption, dose held, or discontinuation)
Measured: Up to 90 days post end of treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Sep 2026
- Study startSep 2026 (estimated)
- Primary completionMar 2028 (estimated)
- Study completionMar 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Head and Neck Squamous Cell CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 160 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Bicara Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07807163
- Sponsor's protocol ID
- BCA101X201
- Other IDs
- 2026-526741-10-00
- Acronym
- FORTIFI-FLEX
- Status last verified
- Oct 2026
- First submitted
- 18 Aug 2026
- Last updated
- 13 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided