临床试验/2024-519654-37-00

2024-519654-37-00招募中3 期

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.

Bicara Therapeutics Inc.81 个研究点分布在 7 个国家目标入组 191 人开始时间: 2025年10月6日最近更新: 2025年10月13日

试验速览

阶段: 3 期
状态: 招募中
发起方
入组人数: 191
试验地点: 81
主要终点: Phase 2 (Dose Selection) - Safety: Incidence and severity of TEAEs, treatment-emergent SAEs.

研究概览研究设计入排标准结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

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.

研究设计

分配方式: Randomized
主要目的: Phase 3
盲法: Double (Analyst, Investigator, Monitor, Subject)

入排标准

年龄范围: 18 years 至 65+ years（65+ Years, 18-64 Years）
接受健康志愿者: 否

入选标准

•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 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. Hepatic • Total serum bilirubin ≤1.5 x upper limit of normal (ULN) (except for subjects with documented Gilbert’s syndrome). • AST (SGOT) and ALT (SGPT) ≤2.5xULN OR ≤5xULN for subjects with liver metastases. Coagulation • INR, PT, 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 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.
•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 should agree to use a condom and to not donate sperm starting with the first dose of study treatment through after the last dose of study medication.
•Subject is ≥18 years of age 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; and completed systemic therapy >6 months prior if given as part of multimodal treatment for locoregionally advanced disease in the adjuvant or definitive setting.
•Subject is willing to provide archival tumor tissue (a paraffin-embedded tumor tissue block sufficient to obtain 20 sections of 4 to 10 micrometer thickness) 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.

排除标准

•Prior systemic therapy in the recurrent or metastatic setting.
•Subjects who are at higher risk of bleeding including subject with known bleeding diathesis, or have current active major bleeding, or a recent major bleeding episode within 4 weeks prior to enrollment. Note: A major bleeding episode is defined according to the International Society on Thrombosis and Haemostasis (ISTH) 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.
•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 congestive heart failure. Subjects with deep vein thrombosis that 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.
•Subject 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 half live of the agent received is not known before enrollment.
•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 study 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.
•Disease suitable for local therapy administered with curative intent.
•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.
•Prior treatment with anti-TGFβ 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 inhibitor 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, or 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.

结局指标

主要结局

Phase 2 (Dose Selection) - Safety: Incidence and severity of TEAEs, treatment-emergent SAEs.

Phase 2 (Dose Selection) - Tolerability: TEAEs leading to dose interruption, dose reduction or permanent discontinuation.

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.

Phase 3 - OS: Defined as the time from the randomization to death due to any cause.

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).

次要结局

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.
Phase 3 - Safety: Incidence and severity of TEAEs, and treatment-emergent SAEs.
Phase 3 - Tolerability: TEAEs leading to dose interruption, dose reduction, or permanent discontinuation.
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.
Phase 3 - ORR: Defined as confirmed CR + PR per RECIST 1.1 by BICR. (FAS).
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.
Phase 3 - Clinical Benefit Rate: For subject who demonstrated CR + PR + SD>6 months per RECIST 1.1 by BICR. (FAS).
Phase 3 - ORR, DOR, and PFS per RECIST 1.1 as determined by investigator’s assessment.
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.

研究者

发起方

Bicara Therapeutics Inc.

申办方类型

Pharmaceutical company

责任方

Principal Investigator

主要研究者

Clinical Operations

Scientific

Bicara Therapeutics Inc.

研究点 (81)

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