NCT07129018尚未招募2 期
A Prospective, Open-Label, Multicenter Phase II Clinical Study of Trastuzumab Rezetecan Combined With Pertuzumab and Iparomlimab and Tuvonralimab as First-Line Therapy for HER2-Expressing Locally Advanced or Metastatic Biliary Tract Cancer
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology0 个研究点目标入组 63 人开始时间: 2025年11月1日最近更新:
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 63
- 主要终点
- Objective Response Rate (ORR) by RECIST1.1
研究概览
简要总结
Based on unmet clinical needs, relevant research backgrounds, and scientific evidence, it is planned to conduct a prospective, dual-cohort exploratory study. The aim of this study is to explore the efficacy and safety of ricartuzumab combined with pertuzumab and epalrestat-vorolizumab in the first-line treatment of HER2-expressing locally advanced or metastatic biliary tract cancer. It is expected to provide more treatment options for biliary tract cancer patients, optimize treatment strategies, and improve patients' long-term survival rates.
详细描述
The aim of this study is to explore the efficacy and safety of ricartuzumab combined with pertuzumab and epalrestat-vorolizumab in the first-line treatment of HER2-expressing locally advanced or metastatic biliary tract cancer. It is expected to provide more treatment options for biliary tract cancer patients, optimize treatment strategies, and improve patients' long-term survival rates.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must voluntarily participate in the trial, provide fully informed consent with signed written documentation, and demonstrate good compliance.
- •Age between 18 and 75 years (inclusive), calculated as of the day of signing the informed consent form; both male and female patients are eligible.
- •Patients must have histologically or cytologically confirmed locally advanced or metastatic biliary tract cancer, including: Cholangiocarcinoma (intrahepatic or extrahepatic) and Gallbladder carcinoma
- •HER2 Expression Criteria: HER2 Overexpression: IHC 3+ OR IHC 2+ with FISH-positive (gene amplification); HER2 Moderate/Low Expression: Moderate: IHC 2+ with FISH-negative (no gene amplification) Low: IHC 1+ (any level of HER2 staining)
- •Patients must not have received prior systemic anti-tumor therapy for advanced disease. Prior neoadjuvant/adjuvant chemotherapy and/or radiotherapy is permitted, provided ≥6 months have elapsed between the last dose and disease recurrence.
- •Patients must have at least one measurable lesion meeting RECIST v1.1 criteria, and the lesion must be suitable for repeated accurate measurements.
- •ECOG performance status of 0 or 1;
- •estimated life expectancy ≥12 weeks;
- •Adequate organ and bone marrow function meeting all criteria below (within 14 days prior to treatment initiation):
- •Hematological Tests *(No transfusion, G-CSF use, or corrective medication within 14 days before screening)* Hemoglobin (Hb) ≥90 g/L Absolute Neutrophil Count (ANC) ≥1.5 × 10<sup>9</sup>/L Platelets (PLT) ≥75 × 10<sup>9</sup>/L
- •Biochemical Tests (No albumin infusion within 14 days before screening) Total Bilirubin (TBIL) ≤2 × ULN Gilbert's syndrome: ≤3 × ULN ALT/AST ≤3.0 × ULN Liver metastasis: ≤5 × ULN Serum Creatinine (Cr) ≤1.5 × ULN OR Creatinine Clearance (CrCl) ≥50 mL/min (Cockcroft-Gault formula);
- •Patients with detectable HBV DNA levels (≥10 IU/mL or above the lower limit of quantification per local laboratory assays) who are HBV-infected (HBsAg-positive and/or anti-HBc-positive) must receive antiviral therapy prior to treatment initiation according to institutional practice to achieve sufficient viral suppression. Antiviral therapy must be maintained throughout the study and for 6 months after the last dose of study treatment. Patients with positive anti-HBc but undetectable HBV DNA (<10 IU/mL or below the lower limit of quantification per local laboratory assays) do not require antiviral prophylaxis unless HBV DNA exceeds 10 IU/mL or reaches detectable levels during treatment monitoring.
- •Childbearing potential females: Negative pregnancy test (urine/serum) within 7 days pre-dose (serum result definitive if urine inconclusive). Sexually active with non-sterilized males: Use acceptable contraception from screening until 120 days post-last dose.
- •Non-sterilized males sexually active with childbearing-potential partners: Use effective contraception from screening until 120 days post-last dose. Discontinuation post-120 days requires investigator discussion.
- •Subjects must comply with visits, treatment, lab tests, and study requirements.
排除标准
- •Histologically or cytologically confirmed ampullary carcinoma, small cell carcinoma, neuroendocrine tumors, sarcoma, mucinous cystic neoplasms, or other rare biliary tract malignancies.
- •Active other malignancies within 5 years or concurrently.
- •History of leptomeningeal disease, brain metastases, or current brain metastases.
- •Participation in other investigational drug trials within the past 3 months, or concurrent enrollment in another interventional clinical trial (observational/non-interventional studies or follow-up phases allowed).
- •Any condition deemed by the investigator to compromise safety or compliance, including: Uncontrolled systemic diseases (e.g., severe hypertension, moderate/severe symptomatic ascites) Uncontrolled/moderate-or-greater pleural/pericardial effusion Acute/chronic uncontrolled pancreatitis Active bleeding disorders, infections, or ILD/interstitial lung disease Severe chronic GI disorders with diarrhea Psychiatric illness/social circumstances affecting compliance History of allogeneic organ or bone marrow transplantation.
- •Within 12 months prior: NYHA Class ≥II congestive heart failure Unstable angina, myocardial infarction Poorly controlled arrhythmia or cerebrovascular accident LVEF <50% by echocardiogram QTc >480 ms (Fridericia method; average of 3 measurements if abnormal) Uncontrolled hypertension (SBP≥150 mmHg and/or DBP≥100 mmHg, average of ≥2 readings) History of hypertensive crisis or encephalopathy.
- •Active autoimmune disease within 2 years or history of recurrent autoimmune disease (e.g., autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hypophysitis, vasculitis, nephritis, hyper/hypothyroidism). (Except hypothyroidism controlled by hormone replacement)
- •Previous treatment with HER2-targeted agents, HER2-ADCs, or immunotherapy (e.g., checkpoint inhibitors/agonists, cell therapy). Therapeutic cancer vaccines excluded.
- •Prior anti-tumor therapy toxicities not recovered to CTCAE v5.0 Grade ≤1 (alopecia/lab abnormalities meeting inclusion criteria allowed per investigator).
- •Unexplained intra-abdominal gas unrelated to recent surgery/paracentesis.
- •Abdominal complications within 6 months: Abdominal fistula, gastrointestinal perforation, or abscess；Tumor invasion of adjacent organs (e.g., aorta, trachea) with high bleeding/fistula risk.
- •Immunodeficiency (e.g., HIV infection) or history of organ transplantation.
- •Active tuberculosis (TB): Active TB within 1 year prior to enrollment；Untreated active TB history >1 year prior.
- •Bleeding/thrombotic risks: Gastrointestinal bleeding within 6 months or high bleeding tendency；Known hereditary/acquired bleeding disorders or thrombophilia.
- •Surgical history: Major surgery within 4 weeks prior (excluding biopsies) or unhealed surgical wounds ；Planned major surgery during the study；Minor traumatic surgery within 7 days prior；
- •Severe/unhealed wounds, active ulcers, or untreated fractures.
- •CNS metastases (past or present).
- •Live attenuated vaccines: Administered within 28 days before the first study dose; Planned use during the study or within 60 days after the last dose.
- •Other exclusionary factors per investigator judgment (e.g., substance abuse, severe comorbidities, abnormal lab values, psychosocial circumstances).
研究组 & 干预措施
HER2 Overexpression Cohort
Experimental
HER2 Overexpression ：IHC 3+ or IHC 2+/FISH +；
干预措施: Trastuzumab-rezetecan + Pertuzumab + Iparomlimab and Tuvonralimab for HER2 Overexpression BTC (Drug)
HER2 Moderate/Low Expression Cohort
Experimental
HER2 Moderate/Low Expression：IHC 2+/FISH -（Moderate Expression）IHC 1+（Low Expression）；
干预措施: Trastuzumab-rezetecan + Pertuzumab + Iparomlimab and Tuvonralimab for HER2 Moderate/Low BTC (Drug)
结局指标
主要结局
Objective Response Rate (ORR) by RECIST1.1
时间窗: Up to approximately 4 years
Objective Response Rate (ORR) assessed by investigators based on the Response EvaluationCriteria in Solid Tumors version 1.1 (RECIST v1.1).
次要结局
- PFS(Up to approximately 4 years)
- Incidence of Adverse Events (AEs)(Up to approximately 4 years)
- Objective Response Rate (ORR) by mRECIST(Up to approximately 4 years)
- DCR(Up to approximately 4 years)
- OS(Up to approximately 4 years)
- TTP(Up to approximately 4 years)
- DoR(Up to approximately 4 years)
研究者
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