Evaluation of Ficerafusp Alfa and Pembrolizumab Combination in PD-L1-positive Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma
- Trial ID
- 2024-519654-37-00
- Protocol
- BCA101X301
- Sponsor
- Bicara Therapeutics Inc.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of the Phase 2 component is to determine the optimal biological dose of ficerafusp alfa by evaluating safety, tolerability, and antitumor activity in subjects receiving either 1500 mg or 750 mg weekly in combination with pembrolizumab. The Phase 3 primary objective is to evaluate the efficacy of the selected optimal biological dose of ficerafusp alfa combined with pembrolizumab compared to placebo plus pembrolizumab in patients with head and neck squamous cell carcinoma. Secondary objectives include:
- Further comparison of antitumor activity in the Phase 2 dose-selection cohort.
- Comparison of safety and tolerability in the Phase 3 cohort.
- Further evaluation of efficacy in the Phase 3 cohort.
- Assessment of time to deterioration regarding pain and quality of life or global health status.
Participants
This clinical trial involves 460 participants diagnosed with recurrent or metastatic head and neck squamous cell carcinoma. The study population includes both male and female individuals aged 18 years or older. Eligible participants must demonstrate measurable disease according to RECIST 1.1 and possess an ECOG performance status of 0 or 1. Inclusion requires documented HPV-negative status for oropharyngeal squamous cell carcinoma and a PD-L1 expression of CPS ≥1. Candidates must have adequate hematological, renal, hepatic, and coagulation function. Furthermore, participants must have had no prior systemic therapy in the recurrent or metastatic setting, with certain exceptions for multimodal treatments completed more than 6 months prior. Women of childbearing potential and male subjects are required to adhere to specific contraception or abstinence protocols.
Plans and Procedures
This multicenter, randomized, double-blind, Phase 2/3 study evaluates the efficacy and safety of ficerafusp alfa in combination with pembrolizumab compared to placebo plus pembrolizumab for the first-line treatment of recurrent or metastatic head and neck squamous cell carcinoma. The Phase 2 portion focuses on dose selection by assessing the safety, tolerability, and antitumor activity of two different doses of ficerafusp alfa administered weekly. The Phase 3 portion aims to compare the efficacy of the selected optimal biological dose in combination with pembrolizumab against the placebo group. The study procedures begin with a screening visit to confirm eligibility through histological verification, PD-L1 expression testing, and assessment of organ function. Following randomization, participants receive treatments via intravenous infusion. The trial includes follow-up assessments to monitor overall survival, progression-free survival, and objective response rate. Study involvement is expected to continue through the completion of the treatment and subsequent follow-up periods. Early termination from the study may occur due to disease progression, occurrence of serious adverse events, or other clinical conditions necessitating discontinuation.
Treatment
Ficerafusp alfa is an experimental investigational product administered as a solution for infusion. The available pharmaceutical forms include a vial for intravenous use and a powder for concentrate for solution for infusion. In this clinical trial, the study evaluates doses of 1500 mg or 750 mg administered via intravenous use on a once weekly schedule.
Pembrolizumab is used as a comparator or in combination with the experimental therapy. The treatment is provided as a solution for infusion, specifically as a 25 mg/mL concentrate, at a dose of 200 mg via intravenous use.
A saline bag is utilized as a placebo in certain treatment arms of the study.
Efficacy
In this study evaluating the treatment of head and neck squamous cell carcinoma, efficacy assessment is divided into Phase 2 and Phase 3 components. For the Phase 2 dose selection stage, the primary efficacy endpoint is the objective response rate (ORR), defined as the proportion of subjects in the dose-selection set achieving a confirmed complete response (CR) or partial response (PR) as determined by blinded independent central review (BICR) using RECIST 1.1 criteria after at least 12 weeks of follow-up. The secondary endpoint for Phase 2 is duration of response (DOR), measured from the first documented CR or PR until disease progression or death per RECIST 1.1 by BICR.
The Phase 3 component utilizes overall survival (OS), defined as the time from randomization to death from any cause, as a primary endpoint. Secondary efficacy endpoints in Phase 3 include ORR, evaluated by BICR, and progression-free survival (PFS), defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 by BICR or death from any cause. Additional secondary parameters include DOR and the clinical benefit rate, which includes subjects achieving CR, PR, or stable disease (SD) lasting longer than 6 months. Efficacy is also assessed via investigator's assessment for ORR, DOR, and PFS. Quality of life measures include time to deterioration (TTD) in global health status and pain, evaluated using EORTC QLQ C30 and EORTC HN 35 instruments.
Inclusion and Exclusion Criteria
Inclusion Criteria
- 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.
- 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.
- 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.
- 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.
- Subject is willing to provide archival tumor tissue or willing to undergo pretreatment biopsy at Screening if archival tissue is insufficient or unavailable.
- 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.
- 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.
- 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.
- Subject has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- 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
- 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.
- 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.
- 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
- Prior systemic therapy in the R or M setting.
- Disease suitable for local therapy administered with curative intent.
- Prior treatment with anti-TGF-β therapy.
- Prior therapy with an anti-EGFR antibody
- Prior history of Grade ≥2 intolerance or hypersensitivity reaction.
- Prior (neoadjuvant and/or adjuvant) therapy with an immune checkpoint inhibitors completed within 6 months prior to study treatment initiation.
- PD (radiologically or pathologically confirmed) <6 months from completion of curative intent systemic therapy for locoregionally advanced HNSCC.
- Life expectancy of less than 3 months and/or has rapidly progressing disease in the treating investigator's opinion.
- 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
- 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
- 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.
- 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.
- 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.
- 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.
- 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.
- Known psychiatric, behavioral, or substance abuse disorders that would interfere with cooperation of the study requirements.
- 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.
- 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.
- Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies). HIV testing is not required unless mandated by local health authority.
- 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 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.
- 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.
- Use of a live or live attenuated vaccine within 4 weeks prior to Screening. Note: Administration of killed, recombinant or inactivated vaccines is allowed.
- Active pregnancy or breastfeeding.
- History of (noninfectious) pneumonitis/interstitial lung disease or has current pneumonitis/interstitial lung disease.
- 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.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Austria | Recruiting | 01 Nov 2025 | 6 |
 Belgium | Recruiting | 01 Nov 2025 | 12 |
 Czechia | Recruiting | 01 Nov 2025 | 6 |
 France | Recruiting | 01 Nov 2025 | 22 |
 Germany | Recruiting | 01 Nov 2025 | 35 |
 Greece | Recruiting | 01 Nov 2025 | 8 |
 Ireland | Recruiting | 01 Nov 2025 | 10 |
 Italy | Recruiting | 01 Nov 2025 | 53 |
 Poland | Recruiting | 01 Nov 2025 | 20 |
 Portugal | Recruiting | 01 Nov 2025 | 21 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
KEYTRUDA 25 mg/mL concentrate for solution for infusion | Test | CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS USE | 200 | 24 | PRD4323105 |
KEYTRUDA 25 mg/mL concentrate for solution for infusion | Test | CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS USE | 200 | 24 | PRD4323786 |
KEYTRUDA 25 mg/mL concentrate for solution for infusion | Test | CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS USE | 200 | 24 | PRD4323784 |
Ficerafusp Alfa | Test | VIAL FOR INTRAVENOUS USE | SOLUTION FOR INFUSION | 1500 | 24 | PRD12408372 |
KEYTRUDA 25 mg/mL concentrate for solution for infusion | Test | CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS USE | 200 | 24 | PRD12081134 |
KEYTRUDA 25 mg/mL concentrate for solution for infusion | Test | CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS USE | 200 | 24 | PRD12081135 |
KEYTRUDA 25 mg/mL concentrate for solution for infusion | Test | CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS USE | 200 | 24 | PRD12081132 |
KEYTRUDA 25 mg/mL concentrate for solution for infusion | Test | CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS USE | 200 | 24 | PRD4323785 |
Saline bag | Placebo | N/A | — | — | — | N/A |
KEYTRUDA 25 mg/mL concentrate for solution for infusion | Test | CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS USE | 200 | 24 | PRD12081133 |