HAIC + DEB-TACE + Toripalimab + Lenvatinib for Unresectable Intrahepatic Cholangiocarcinoma

NCT07685535 | Not Yet Recruiting Phase 2

• 1 other identifier: MATCH-002
• Study Type: interventional
• Target: 29
• Locations: 0 countries
• Sites: N/A

Brief Summary

Purpose: This phase II clinical trial evaluates whether a combination of liver-directed local therapies (HAIC and DEB-TACE) with immunotherapy (toripalimab) and targeted therapy (lenvatinib) is safe and effective for patients with unresectable intrahepatic cholangiocarcinoma (a type of liver cancer that cannot be removed by surgery). Participants: Adults aged 18-85 years with pathologically confirmed unresectable intrahepatic cholangiocarcinoma, no prior immune checkpoint inhibitor therapy, and adequate organ function. Study details include: Study Duration: Up to 24 months per participant Treatment Duration: Up to 6 cycles (each cycle is 21 days) of combination therapy, followed by maintenance therapy with toripalimab and lenvatinib until disease progression or unacceptable toxicity Visit Frequency: Every 3 weeks during the treatment phase; tumor imaging assessments every 6-8 weeks Primary endpoints: Objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Safety will be assessed by monitoring adverse events graded according to NCI-CTCAE v5.0. Toripalimab and lenvatinib are not available through an expanded access program.

Conditions

Liver Cancer

Outcome Measures

Primary Outcomes (3)

• Objective Response Rate (ORR)

  Proportion of participants achieving a confirmed complete response (CR) or partial response (PR) according to RECIST 1.1 and mRECIST criteria, assessed by the investigator. This is the primary efficacy endpoint used for sample size calculation.

  From the start of treatment until disease progression, up to 24 months

• Progression-Free Survival (PFS)

  Time from enrollment to first documented disease progression per RECIST 1.1 and mRECIST criteria, or death from any cause, whichever occurs first.

  From enrollment until disease progression or death, assessed up to 24 months

• Overall Survival (OS)

  Time from enrollment to death from any cause.

  From enrollment until death, assessed up to 24 months

Secondary Outcomes (3)

• Disease Control Rate (DCR)

  From the start of treatment until disease progression, up to 24 months

• Duration of Response (DoR)

  From first response until disease progression or death, assessed up to 24 months

• Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)

  From the time of informed consent until 30 days after the last dose of study treatment, or until resolution/return to baseline, assessed up to 24 months

Study Arms (1)

HAIC + DEB-TACE + Toripalimab + Lenvatinib

EXPERIMENTAL

Participants receive a combination regimen consisting of: HAIC (Hepatic Arterial Infusion Chemotherapy): Oxaliplatin 85 mg/m² and gemcitabine (total 1000 mg/m², with a portion used for DEB-TACE loading) administered via hepatic artery infusion on Day 1 of each 21-day cycle, for up to 6 cycles. DEB-TACE (Drug-Eluting Beads Transarterial Chemoembolization): Small-sized (40-90 μm) drug-eluting beads loaded with gemcitabine, performed on Day 1 of each cycle as needed (required in Cycle 1, thereafter based on tumor vascularity and imaging assessment). Toripalimab: 200 mg intravenous infusion on Day 1 of each 21-day cycle. Lenvatinib: Oral daily dosing (8 mg/day for body weight \<60 kg; 12 mg/day for body weight ≥60 kg), continued throughout the study. After completion of up to 6 cycles, patients without disease progression enter a maintenance phase receiving toripalimab plus lenvatinib until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to t

Device: DEB-TACE; Drug: Toripalimab; Drug: Lenvatinib; Drug: Gemcitabine; Drug: Oxaliplatin

Interventions

DEB-TACE DEVICE

Small-sized (40-90 μm) drug-eluting beads loaded with gemcitabine, administered via transarterial chemoembolization into the hepatic artery to occlude tumor blood vessels and deliver localized chemotherapy. Performed on Day 1 of each 21-day cycle as needed (required in Cycle 1, thereafter based on tumor vascularity and imaging assessment).

HAIC + DEB-TACE + Toripalimab + Lenvatinib

Toripalimab DRUG

200 mg administered as an intravenous infusion on Day 1 of each 21-day cycle. Toripalimab is a humanized anti-PD-1 monoclonal antibody that blocks PD-1/PD-L1 interaction, restoring T-cell anti-tumor immune activity.

HAIC + DEB-TACE + Toripalimab + Lenvatinib

Lenvatinib DRUG

Oral daily dosing: 8 mg/day for body weight \<60 kg; 12 mg/day for body weight ≥60 kg. Lenvatinib is a multi-target tyrosine kinase inhibitor that inhibits VEGFR1-3, FGFR1-4, PDGFRα, KIT, and RET, thereby reducing tumor angiogenesis and suppressing tumor cell proliferation.

HAIC + DEB-TACE + Toripalimab + Lenvatinib

Gemcitabine DRUG

Total dose 1000 mg/m² administered via hepatic artery infusion (HAIC) on Day 1 of each 21-day cycle, for up to 6 cycles. A portion of the dose is used for DEB-TACE drug loading; the remainder is administered via HAIC. Gemcitabine is a pyrimidine nucleoside analog that inhibits DNA synthesis and induces tumor cell apoptosis.

HAIC + DEB-TACE + Toripalimab + Lenvatinib

Oxaliplatin DRUG

85 mg/m² administered via hepatic artery infusion (HAIC) on Day 1 of each 21-day cycle, for up to 6 cycles. Oxaliplatin is a third-generation platinum-based chemotherapeutic agent that forms DNA crosslinks, blocking DNA replication and transcription, and inducing tumor cell apoptosis.

HAIC + DEB-TACE + Toripalimab + Lenvatinib

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntary participation and signed informed consent.
• Age 18 to 85 years.
• Pathologically confirmed intrahepatic cholangiocarcinoma.
• Imaging-confirmed unresectable locally advanced intrahepatic cholangiocarcinoma with measurable lesions (longest diameter ≥10 mm) per RECIST 1.1.
• No distant organ metastases (excluding lymph node metastases).
• Child-Pugh liver function grade A or good B (≤7 points).
• ECOG performance status score 0-1 within 1 week before enrollment.
• Expected survival ≥12 weeks.
• No prior treatment with immune checkpoint inhibitors (including PD-1/PD-L1 antibodies and CTLA-4 inhibitors).
• Laboratory values within 7 days before enrollment meeting the following criteria:
• ANC ≥1.0×10⁹/L; platelets ≥50×10⁹/L; hemoglobin ≥90 g/L (without transfusion or G-CSF within 14 days before screening).
• Serum albumin ≥30 g/L; total bilirubin ≤1.5×ULN; ALT and AST ≤5×ULN; serum creatinine ≤1.5×ULN or CrCl \>50 mL/min (Cockcroft-Gault formula).
• INR ≤2.3 or PT prolonged ≤6 seconds above normal range.
• Urine protein \<2+ (if ≥2+, 24-hour quantification \<1.0 g allowed).

You may not qualify if:

• Received other local treatments (excluding surgery) within 1 month before study entry. Prior TAE/TAI not allowed. Prior TACE \>3 times not allowed.
• Prior systemic anti-tumor therapy (including targeted therapy, immunotherapy, chemotherapy).
• Concurrent or prior other malignancy within 5 years.
• Active autoimmune disease or history of autoimmune disease with potential relapse.
• Clinically symptomatic moderate-to-severe ascites requiring therapeutic paracentesis/drainage or Child-Pugh score \>2; uncontrolled or moderate-to-large pleural/pericardial effusion.
• History of abdominal fistula, GI perforation, or intra-abdominal abscess within 6 months before study treatment.
• History of thrombosis or embolic events (e.g., cerebrovascular accident including TIA, cerebral hemorrhage, cerebral infarction, pulmonary embolism) within 6 months before study treatment.
• Known inherited or acquired bleeding disorder or thrombotic tendency; currently or recently (within 10 days) receiving full-dose anticoagulants or thrombolytics for therapeutic purposes (prophylactic low-dose aspirin or LMWH allowed).
• Major vascular disease within 6 months before study treatment (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis).
• Severe, non-healing, or dehisced wounds, active ulcers, or untreated fractures.
• Major surgery within 4 weeks before study treatment (excluding diagnostic) or anticipated need for major surgery during the study.
• History of intestinal obstruction or clinical signs/symptoms of GI obstruction within 6 months before study treatment.
• History of hepatic encephalopathy.
• Palliative radiotherapy for non-target lesions allowed only if completed ≥2 weeks before study treatment and AEs recovered to ≤CTCAE grade 1.
• Severe infection within 4 weeks before study treatment, including hospitalization for infection, bacteremia, or severe pneumonia; oral or IV therapeutic antibiotics within 2 weeks (prophylactic allowed).

Sponsors & Collaborators

• Shanghai Zhongshan Hospital: lead

MeSH Terms

Conditions

Liver Neoplasms

Interventions

toripalimab; lenvatinib; Gemcitabine; Oxaliplatin

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Coordination Complexes; Organic Chemicals

Study Design

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

Model Details: This is a single-arm, open-label study in which all participants will receive the same combination treatment regimen consisting of HAIC, DEB-TACE, toripalimab, and lenvatinib. No comparator or control group is included.

Study Record Dates

• First Submitted: June 28, 2026
• First Posted: July 6, 2026
• Study Start: June 30, 2026
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: July 6, 2026

Record last verified: 2026-06