HAIC Plus QL1706 & Bevacizumab in Unresectable HER2-Negative ICC

NCT07841574 | Recruiting Phase 2

• 1 other identifier: SL-B2026-248-01
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Intrahepatic Cholangiocarcinoma

Keywords

Intrahepatic Cholangiocarcinoma; FOLOFX-HAIC; QL1706

Outcome Measures

Primary Outcomes (1)

• objective response rate，ORR

  ORR was defined as the proportion of patients achieving best overall response of complete response (CR) or partial response (PR) per RECIST 1.1.

  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.

Secondary Outcomes (4)

• 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.

Other Outcomes (1)

• Exploratory Biomarker Analysis

  From screening up to 24 months after the first dose of study treatment.

Study Arms (1)

Hepatic Arterial Infusion Chemotherapy (HAIC) Combine QL1706 and bevacizumab

EXPERIMENTAL

Drug: hepatic arterial infusion chemotherapy (HAIC) combine with QL1706 and bevacizumab

Interventions

hepatic arterial infusion chemotherapy (HAIC) combine with QL1706 and bevacizumab DRUG

Eligible patients were treated with HAIC plus QL1706 and bevacizumab. On the treatment day, continuous hepatic artery chemotherapy infusion was administered via an indwelling catheter connected to a micro-infusion pump. The infusion regimen included oxaliplatin 130 mg/m² over 3 hours, leucovorin 400 mg/m² over 1.5 hours, 5-FU 400 mg/m² over 2 hours, and 5-FU 2400 mg/m² over 46 hours. The catheter was removed after infusion completion. On the subsequent morning, patients received intravenous QL1706 (7.5 mg/kg) and bevacizumab (15 mg/kg), and were discharged after infusion. Treatment was repeated every 3-4 weeks for up to six cycles. Patients with favorable responses received continuous systemic maintenance therapy. Maintenance treatment was continued until death, intolerable toxicity, or loss of clinical benefit, with therapeutic regimens adjusted according to individual clinical status.

Also known as: HAIC, QL1706, Bevacizumab

Hepatic Arterial Infusion Chemotherapy (HAIC) Combine QL1706 and bevacizumab

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Age ≥18 years and ≤75 years. 2. Good general condition with Eastern Cooperative Oncology Group Performance Status (ECOG-PS) score of 0-1.
• \. Histopathologically or cytopathologically confirmed intrahepatic cholangiocarcinoma (ICC).
• \. No prior anti-tumor treatment for intrahepatic cholangiocarcinoma. 5. 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.
• \. Laboratory test results meet the following criteria (or achievable after short-term medical intervention):
• \. Absolute neutrophil count ≥ 2.0 × 10⁹/L 2. Hemoglobin ≥ 100 g/L 3. Platelet count ≥ 75 × 10⁹/L 4. Plasma albumin ≥ 35 g/L 5. Total serum bilirubin \< 2 × upper limit of normal (ULN) 6. Alanine aminotransferase (ALT) \< 3 × ULN 7. Aspartate aminotransferase (AST) \< 3 × ULN 8. Serum creatinine \< 1.5 × ULN 9. Prothrombin time is normal or no more than 4 seconds above the ULN 10. International normalized ratio (INR) ≤ 2.2 7. Subjects fully understand the study and provide written informed consent. 8. Child-Pugh score ≤ 6 (Child-Pugh A class). 9. At least one measurable lesion per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).
• \. 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.
• \. Expected survival ≥ 12 weeks. 12. No history of autoimmune diseases.

You may not qualify if:

• \. 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.
• \. History of other malignant neoplasms. 3. History of allergic reactions to relevant study drugs. 4. Known hypersensitivity to any component of iparomlimab-tuvonralimab or to other monoclonal antibody agents.
• \. History of solid-organ transplantation. 6. Prior anti-tumor therapy (including interferon) for ICC. 7. Human immunodeficiency virus (HIV) infection. 8. History of drug abuse or illicit-drug use. 9. Gastrointestinal hemorrhage or cardiovascular/cerebrovascular events within 30 days prior to enrolment.
• \. Pregnant or lactating women; women of child-bearing potential unwilling to adopt contraceptive measures.
• \. Psychiatric disorders that preclude informed consent or proper study participation.
• \. Brain metastases, or bone metastases requiring urgent surgical or radiotherapy intervention.
• \. 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.
• \. 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.
• \. Administration of live vaccines within 4 weeks prior to study drug initiation or planned live-vaccine administration during study participation.
• \. 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.
• \. 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.
• \. Uncorrectable coagulopathy or marked hematologic abnormalities with clear bleeding tendency (e.g. hemophilia, coagulation disorders, severe thrombocytopenia).
• \. ECOG-PS score ≥ 2. 20. Child-Pugh score ≥ 7 (Child-Pugh B or C class). 21. 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.
• \. Uncontrolled hypertension despite antihypertensive medication (systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg).
• \. HER2-positive tumor status. 24. Any other conditions that, in the investigator's opinion, may interfere with subject enrolment or endpoint assessment.

Sponsors & Collaborators

• Lianghe Lu: lead

Study Sites (1)

Sun Yat-sen university cancer center

Guangzhou, Guangdong, 510060, China

RECRUITING

MeSH Terms

Conditions

Cholangiocarcinoma

Interventions

Bevacizumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Rongping Guo, Pro.

CONTACT

+86 20 8734 2266; guorp@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: September 21, 2026
• First Posted: September 25, 2026
• Study Start: June 11, 2026
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): June 30, 2029
• Last Updated: September 25, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)