NCT07841574招募中2 期
Hepatic Arterial Infusion Chemotherapy Combined With Iparomlimab/Tuvonralimab (QL1706) and Bevacizumab in Patients With Unresectable HER2-Negative Intrahepatic Cholangiocarcinoma:A Prospective Phase II Study
Lianghe Lu1 个研究点 分布在 1 个国家目标入组 35 人开始时间: 2026年6月11日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 35
- 试验地点
- 1
- 主要终点
- objective response rate，ORR
研究概览
简要总结
Intrahepatic cholangiocarcinoma (ICC) has an increasing global incidence, and over 70% of patients are diagnosed at unresectable stages with limited survival benefits from standard first-line chemotherapy regimens. Hepatic arterial infusion chemotherapy (HAIC) delivers high-concentration local chemotherapy to liver tumors, while the PD-1/CTLA-4 dual antibody iparomlimab and tuvonralimab (QL1706) combined with bevacizumab can reshape the immunosuppressive tumor microenvironment and exert synergistic anti-tumor effects.The purpose of this study is to evaluate the efficacy and safety of HAIC-FOLFOX plus QL1706 and bevacizumab as first-line therapy for patients with unresectable HER2-negative intrahepatic cholangiocarcinoma.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •1. Age ≥18 years and ≤75 years.
- •Good general condition with Eastern Cooperative Oncology Group Performance Status (ECOG-PS) score of 0-
- •3. Histopathologically or cytopathologically confirmed intrahepatic cholangiocarcinoma (ICC).
- •4. No prior anti-tumor treatment for intrahepatic cholangiocarcinoma.
- •Confirmed as unresectable, non-ablatable and not eligible for other curative-intent therapies after multidisciplinary discussion by the hepatobiliary tumor expert team of this hospital.
- •6. Laboratory test results meet the following criteria (or achievable after short-term medical intervention):
- •1. Absolute neutrophil count ≥ 2.0 × 10⁹/L
- •Hemoglobin ≥ 100 g/L
- •Platelet count ≥ 75 × 10⁹/L
- •Plasma albumin ≥ 35 g/L
- •Total serum bilirubin < 2 × upper limit of normal (ULN)
- •Alanine aminotransferase (ALT) < 3 × ULN
- •Aspartate aminotransferase (AST) < 3 × ULN
- •Serum creatinine < 1.5 × ULN
- •Prothrombin time is normal or no more than 4 seconds above the ULN
- •International normalized ratio (INR) ≤ 2.2
- •Subjects fully understand the study and provide written informed consent.
- •Child-Pugh score ≤ 6 (Child-Pugh A class).
- •At least one measurable lesion per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).
- •10. For women of child-bearing potential (including non-surgically sterilized subjects): use medically-accepted contraception during study treatment and for 3 months after completion of study treatment; serum or urine human chorionic gonadotropin (HCG) test must be negative within 72 hours prior to enrolment; must not be lactating. For male subjects with female partners of child-bearing potential: effective contraception is required during the study and for 3 months after the last dose of iparomlimab-tuvonralimab.
- •11. Expected survival ≥ 12 weeks.
- •No history of autoimmune diseases.
排除标准
- •1. Severe impairment of major organs including heart, brain, lung or kidney; severe infection or other serious comorbidities (CTCAE v5.0 adverse events ≥ Grade 2) rendering the subject intolerant to study treatment.
- •2. History of other malignant neoplasms.
- •History of allergic reactions to relevant study drugs.
- •Known hypersensitivity to any component of iparomlimab-tuvonralimab or to other monoclonal antibody agents.
- •5. History of solid-organ transplantation.
- •Prior anti-tumor therapy (including interferon) for ICC.
- •Human immunodeficiency virus (HIV) infection.
- •History of drug abuse or illicit-drug use.
- •Gastrointestinal hemorrhage or cardiovascular/cerebrovascular events within 30 days prior to enrolment.
- •10. Pregnant or lactating women; women of child-bearing potential unwilling to adopt contraceptive measures.
- •11. Psychiatric disorders that preclude informed consent or proper study participation.
- •12. Brain metastases, or bone metastases requiring urgent surgical or radiotherapy intervention.
- •13. Active autoimmune disease or relevant medical history (including but not limited to autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hypophysitis, vasculitis, nephritis, hyperthyroidism). Note: Subjects with vitiligo; subjects with childhood-onset asthma fully resolved without intervention in adulthood may be enrolled; subjects requiring bronchodilators for asthma are excluded.
- •14. Receiving immunosuppressive agents or systemic corticosteroids for immunosuppressive purposes (prednisone > 10 mg/day or equivalent), and still on such therapy within 2 weeks before enrolment.
- •15. Administration of live vaccines within 4 weeks prior to study drug initiation or planned live-vaccine administration during study participation.
- •16. Other conditions judged by the investigator to interfere with study conduct or subject safety, such as heavy alcohol consumption, substance abuse, severe comorbid illnesses, marked laboratory abnormalities, or family/social circumstances that may compromise subject safety or protocol compliance.
- •17. Clinically significant bleeding episodes or definite bleeding tendency within 3 months before enrolment, e.g. hemoptysis ≥ 2.5 mL, gastrointestinal bleeding, high-risk esophageal-gastric varices, bleeding peptic ulcer, vasculitis. Note: If baseline stool occult blood is positive, repeat testing is required. Persistently positive stool occult blood warrants gastroscopy; subjects with severe esophageal-gastric varices on gastroscopy are excluded. Subjects with gastroscopy performed within the prior 3 months to rule out varices are exempt from repeat gastroscopy.
- •18. Uncorrectable coagulopathy or marked hematologic abnormalities with clear bleeding tendency (e.g. hemophilia, coagulation disorders, severe thrombocytopenia).
- •19. ECOG-PS score ≥
- •Child-Pugh score ≥ 7 (Child-Pugh B or C class).
- •Evidence of hepatic decompensation, e.g. massive ascites, history of upper gastrointestinal bleeding due to esophageal-gastric varices within the past year, hepatic encephalopathy or bilirubin encephalopathy.
- •22. Uncontrolled hypertension despite antihypertensive medication (systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg).
- •23. HER2-positive tumor status.
- •Any other conditions that, in the investigator's opinion, may interfere with subject enrolment or endpoint assessment.
研究组 & 干预措施
Hepatic Arterial Infusion Chemotherapy (HAIC) Combine QL1706 and bevacizumab
Experimental
干预措施: hepatic arterial infusion chemotherapy (HAIC) combine with QL1706 and bevacizumab (Drug)
结局指标
主要结局
objective response rate，ORR
时间窗: From first dose of study treatment until the earliest of progression, death, start of subsequent anti-tumor therapy, or data cutoff, assessed up to 24 months.
ORR was defined as the proportion of patients achieving best overall response of complete response (CR) or partial response (PR) per RECIST 1.1.
次要结局
- disease control rate, DCR(From first dose of study treatment until the earliest of progression, death, start of subsequent anti-tumor therapy, or data cutoff, assessed up to 24 months.)
- progression-free survival, PFS(From date of randomization until the date of first documented progression or death, assessed up to 24 months.)
- Overall survival, OS(From date of first study treatment until death from any cause, assessed up to 36 months.)
- Safety evaluation(From the date of first study treatment until 90 days after the last dose of study treatment.)
研究者
Lianghe Lu
MD
Sun Yat-sen University
研究点 (1)
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