A trial to see if ficerafusp alfa given with pembrolizumab can treat participants with head and neck cancer.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Bicara Therapeutics Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

7 Nov 2025 → ongoing

Decision date (initial)

2025-10-13

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Bicara Therapeutics Inc.

External identifiers

EU CT number

2024-519654-37-00

ClinicalTrials.gov

NCT06788990

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Pharmacokinetic, Therapy, Safety, Efficacy, Dose response

Phase 2 Primary (Dose Selection):
To identify optimal biological dose (OBD) by:
• Assessing safety and tolerability of ficerafusp alfa in subjects randomized to ficerafusp alfa 1500 mg once weekly (QW) with pembrolizumab (Treatment Arm A) and ficerafusp alfa 750 mg QW with pembrolizumab (Treatment Arm B).
• Assessing antitumor activity of ficerafusp alfa in subjects randomized to ficerafusp alfa 1500 mg QW with pembrolizumab (Treatment Arm A) and ficerafusp alfa 750 mg QW and pembrolizumab (Treatment Arm B).

Phase 3 Primary:
• To compare efficacy in subjects treated with ficerafusp alfa at the selected OBD in combination with pembrolizumab versus placebo plus pembrolizumab.

Secondary objectives 4

1. Phase 2 secondary (Dose Selection): To further compare antitumor activity of ficerafusp alfa in subjects randomized to ficerafusp alfa 1500 mg QW with pembrolizumab (Treatment Arm A) and ficerafusp alfa 750 mg QW and pembrolizumab (Treatment Arm B).
2. Phase 3 secondary: To compare safety and tolerability of subjects treated with ficerafusp alfa at the selected OBD in combination with pembrolizumab versus placebo plus pembrolizumab.
3. Phase 3 secondary: To further compare efficacy in subjects treated with ficerafusp alfa in combination with pembrolizumab versus placebo plus pembrolizumab.
4. Phase 3 secondary: To evaluate time to deterioration (TTD) in global health status/quality of life and pain in subjects treated with ficerafusp alfa in combination with pembrolizumab versus placebo plus pembrolizumab.

Conditions and MedDRA coding

Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma.

Study design 2 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. Subject or legally authorized representative, if applicable, has signed and dated informed consent form (ICF) indicating that the subject (or legally authorized representative, if applicable) has been informed of all the pertinent aspects of the study prior to enrollment and the subject must be willing to comply with all study procedures for the duration of the study.
2. Subject is >18 years of age or of an acceptable age according to local regulations, whichever is older on the day the ICF is signed.
3. Subject has 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.
4. No prior systemic therapy administered in the R or M setting. Systemic therapy completed >6 months prior to signing ICF if given as part of multimodal treatment for locoregionally advanced disease is allowed.
5. Subject is willing to provide archival tumor tissue or willing to undergo pretreatment biopsy at Screening if archival tissue is insufficient or unavailable.
6. Subject has documentation of HPV-negative disease per central testing performed if presenting with OPSCC. Tumor tissue from excisional/incisional or core biopsy (fine needle aspirates and bone biopsies are not acceptable) must be provided for central testing. Archival tumor tissue is acceptable. A fresh tumor biopsy, using a procedure that is safe for the subject on a lesion not previously irradiated (unless lesion progressed) will be required if tumor tissue is not available. Note: To be eligible to participate in this study, subjects with OPSCC must have HPV-negative documentation.
7. Subject is eligible to receive pembrolizumab as frontline monotherapy with documented tumor PD-L1 CPS ≥1 (by PD-L1 IHC 22C3 pharmDx assay), determined locally or centrally. If local documentation of PD-L1 is not available, tumor tissue from excisional or core biopsy (fine needle aspirates and bone biopsies are not acceptable) must be provided for central testing to determine eligibility.
8. Subject has measurable disease based on RECIST 1.1 as determined by BICR. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated. Baseline Scan must be transferred to BICR for assessment.
9. Subject has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
10. Subject demonstrates adequate organ function, defined as follows: Hematological • Absolute neutrophil count (ANC) ≥1500/μL • Platelets ≥100,000/μL • Hemoglobin ≥9 g/dL (90 g/L) or ≥5.6 mmol/L. Must be met without packed red blood cell transfusion in the prior 7 days. Renal •Creatinine clearance (CrCl) measured or calculated per institutional standards (CrCl or estimated glomerular filtration rate Hepatic •Total serum bilirubin ≤1.5 x× upper limit of normal (ULN) (except for (Exception: Subjects with documented Gilbert’s syndrome) may be eligible if total bilirubin is ≤3× ULN and direct bilirubin is within normal limits [≤ULN]) •Aspartate aminotransferase (AST ()(SGOT) and alanine aminotransferase (ALT) (SGPT) ≤2.5xULN5× ULN OR ≤5xULN5× ULN for subjects with liver metastases Coagulation •INRInternational normalized ratio, PT, partial thromboplastin time (PTT,), or activated partial thromboplastin time (aPTT) ≤1.5× ULN unless subject is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants
11. Women of childbearing potential (WOCBP) must have a negative blood highly sensitive serum pregnancy test within 7 days prior to receiving the first dose of study treatment. A urine pregnancy test can be considered if a blood test is not appropriate per local standard of care.
12. WOCBP should be willing to use highly effective contraception for birth control or be surgically sterile or abstain from heterosexual activity for the course of the study and are not permitted to donate oocytes during this time. WOCBP are those who have not been surgically sterilized or have not been free from menses for >1 year.
13. Male subjects must agree to use a condom or to remain abstinent (refrain from heterosexual intercourse), and to not donate sperm starting with the first dose of study treatment after the last dose of study medication.

Exclusion criteria 26

1. Prior systemic therapy in the R or M setting.
2. Disease suitable for local therapy administered with curative intent.
3. Prior treatment with anti-TGF-β therapy.
4. Prior therapy with an anti-EGFR antibody
5. Prior history of Grade ≥2 intolerance or hypersensitivity reaction.
6. Prior (neoadjuvant and/or adjuvant) therapy with an immune checkpoint inhibitors completed within 6 months prior to study treatment initiation.
7. PD (radiologically or pathologically confirmed) <6 months from completion of curative intent systemic therapy for locoregionally advanced HNSCC.
8. Life expectancy of less than 3 months and/or has rapidly progressing disease in the treating investigator's opinion.
9. Known active central nervous system metastases, history of spinal cord compression from tumor involvement, a history of carcinomatous meningitis, and leptomeningeal disease are excluded. Subjects with a history of treated central nervous system metastases (by surgery or radiation therapy) may be eligible if central nervous system metastases have been stable for at least 4 weeks, i.e., without evidence of progression by repeat imaging and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment
10. Subjects who are at higher risk of bleeding including subjects with known bleeding diathesis, or who have current active major bleeding, or a recent major bleeding episode within 4 weeks prior to enrolment. Note: A major bleeding episode is defined according to the International Society on Thrombosis and Haemostasis criteria, which include fatal bleeding, symptomatic bleeding in a critical organ/area (e.g., intracranial, intraspinal, intraocular, pericardial, intra-articular, intramuscular with compartment syndrome, retroperitoneal), hemoglobin drop ≥2 g/dL, or transfusion of ≥2 units of blood. •Cases of tumor-related bleeding within the last 4 weeks, or other risk factors potentially increasing the risk of bleeding, should be discussed with the Sponsor Medical Director prior to enrolment
11. Any of the following <6 months before starting study treatment: ST-elevation myocardial infarction, severe/unstable angina, uncontrolled cardiac ventricular arrythmia, coronary/peripheral artery bypass graft or stent, cerebrovascular accident/stroke less than 6 months prior to enrollment or New York Heart Association Class III/IV congestive heart failure. Subjects with deep vein thrombosis who are hemodynamically stable can enroll if they are on a stable dose of anticoagulants for at least 3 months.
12. Major surgery (including eye surgery) or palliative radiotherapy <2 weeks prior to randomization. Subjects must have recovered adequately from any surgery (major or minor) or radiation and/or its complications before randomization.
13. Subjects who 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 or at least 4 weeks if the half-life of the agent received is not known before enrolment.
14. Active autoimmune disease requiring systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
15. Serious systemic infection (bacterial, viral, or fungal) within 4 weeks before first dose of study treatment, or active systemic infection requiring either hospitalization or parenteral anti-infective therapy within 2 weeks before first dose of study treatment.
16. Known psychiatric, behavioral, or substance abuse disorders that would interfere with cooperation of the study requirements.
17. 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 who are hepatitis B surface antigen positive are eligible if they have received HBV antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to randomization. Note: Subjects should remain on antiviral therapy throughout the Treatment period and follow local guidelines for HBV antiviral therapy post completion of study treatment.
18. 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. Note: subjects must have completed curative antiviral therapy at least 4 weeks prior to randomization.
19. Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies). HIV testing is not required unless mandated by local health authority.
20. Receipt of any organ transplantation, including autologous and allogeneic stem cell transplantation, with the exception of transplants that do not require immunosuppression.
21. 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 defined as follows: Stage T1c or T2a with a Gleason score ≤6 and prostatic-specific antigen <10 ng/mL either treated with definitive intent or untreated in active surveillance that has been stable for the past year prior to randomization. Other exceptions may be considered with the Sponsor’s consultation. The time requirement for no malignancy for 2 years does not apply to the cancer for which a subject is enrolled in the study.
22. 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. Corticosteroid use as premedication for allergic reactions (e.g., intravenous contrast), or as a prophylactic management of AEs related to the therapies specified in the protocol is allowed. The use of physiologic doses of corticosteroids may be approved after consultation with the Sponsor.
23. Use of a live or live attenuated vaccine within 4 weeks prior to Screening. Note: Administration of killed, recombinant or inactivated vaccines is allowed.
24. Active pregnancy or breastfeeding.
25. History of (noninfectious) pneumonitis/interstitial lung disease or has current pneumonitis/interstitial lung disease.
26. History of any of the following drug-induced severe cutaneous adverse reactions including, but not limited to, Stevens-Johnson syndrome/toxic epidermal necrolysis, or drug-reaction with eosinophilia and systemic symptoms, or dose-limiting immune-mediated reactions.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 5

1. Phase 2 (Dose Selection) - Safety: Incidence and severity of TEAEs, treatment-emergent SAEs.
2. Phase 2 (Dose Selection) - Tolerability: TEAEs leading to dose interruption, dose reduction or permanent discontinuation.
3. Phase 2 (Dose Selection) - ORR is defined as the proportion of subjects in the DDS who have a confirmed CR or PR per RECIST 1.1. by BICR, at least 12 weeks of follow-up.
4. Phase 3 - OS: Defined as the time from the randomization to death due to any cause.
5. Phase 3 - ORR: Defined as the proportion of the subjects in the FAS who have confirmed CR or PR by BICR per RECIST 1.1. (Subset of FAS).

Secondary endpoints 9

1. Phase 2 - 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.
2. Phase 3 - Safety: Incidence and severity of TEAEs, and treatment-emergent SAEs.
3. Phase 3 - Tolerability: TEAEs leading to dose interruption, dose reduction, or permanent discontinuation.
4. Phase 3 - 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.
5. Phase 3 - ORR: Defined as confirmed CR + PR per RECIST 1.1 by BICR. (FAS).
6. Phase 3 - 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.
7. Phase 3 - Clinical Benefit Rate: For subject who demonstrated CR + PR + SD>6 months per RECIST 1.1 by BICR. (FAS).
8. Phase 3 - ORR, DOR, and PFS per RECIST 1.1 as determined by investigator’s assessment.
9. Phase 3 - The TTD in global health status measured by the EORTC QLQ C30 items for global health status and quality of life scale (item 29/30) and pain measured by the EORTC HN 35 (items 31-34) pain domain.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 10

Comparator 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Bicara Therapeutics Inc.

Sponsor organisation

Bicara Therapeutics Inc.

Address

116 Huntington Avenue Suite 703

City

Boston

Postcode

02116-5784

Country

United States

Scientific contact point

Organisation

Bicara Therapeutics Inc.

Contact name

Clinical Operations

Public contact point

Organisation

Bicara Therapeutics Inc.

Contact name

Clinical Operations

Third parties 15

Locations

11 EU/EEA countries · 89 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 212 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications