A Multicenter Clinical Study of Combined Therapy for Unresectable Hepatocellular Carcinoma

NCT07482059 | Recruiting Phase 1

• 1 other identifier: 20252727
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

This clinical trial was designed to evaluate the safety and efficacy of Y90-SIRT combined with nivolumab, ipilimumab, and lenvatinib in patients with unresectable HCC. In addition to assessing short-term efficacy endpoints, such as ORR and PFS, this trial places particular emphasis on the OS benefit for patients. This study is therefore both novel and innovative.

Conditions

Unresectable Hepatocellular Carcinoma

Keywords

unresectable hepatocellular carcinoma; Yttrium-90 microsphere selective internal radiation therapy (Y90-SIRT); nivolumab; pilimumab; lenvatinib; phase Ib/II study

Outcome Measures

Primary Outcomes (2)

• Incidence of dose-limiting toxicity (DLT) of the quadruple regimen (Y90-SIRT plus nivolumab, ipilimumab, lenvatinib)

  Up to 4 treatment cycles (each cycle is 3 weeks)

• Objective response rate (ORR) assessed by both iRECIST and mRECIST criteria

  24 months

Study Arms (1)

Yttrium-90 microspheres in combination with nivolumab, ipilimumab, and lenvatinib

EXPERIMENTAL

The phase Ib portion of the trial explores the incidence of dose-limiting toxicity (DLT) in the quadruple therapeutic regimen. Three weeks after receiving Y90-SIRT, the patients are assigned to one of three dose exploration cohorts: (1) nivolumab 1 mg/kg IV every 3 weeks (Q3W) + ipilimumab 1 mg/kg IV Q3W for up to 4 cycles; (2) nivolumab 1 mg/kg IV Q3W + ipilimumab 2 mg/kg IV Q3W for up to 4 cycles; (3) nivolumab 1 mg/kg IV Q3W + ipilimumab 3 mg/kg IV Q3W for up to 4 cycles. After completion of ipilimumab administration, nivolumab is continued at 480 mg IV every 4 weeks (Q4W) until disease progression, unacceptable toxicity, withdrawal of informed consent, or a maximum treatment duration of two years. Lenvatinib is then administered after discontinuation of ipilimumab, in combination with nivolumab, at a dose of 8 mg (body weight \<60 kg) or 12 mg (body weight \>60 kg) orally once daily (PO QD), taken at a fixed time each day, with or without food.

Drug: ttrium-90 microspheres in combination with nivolumab, ipilimumab, and lenvatinib in patients with unresectable hepatocellular carcinoma

Interventions

ttrium-90 microspheres in combination with nivolumab, ipilimumab, and lenvatinib in patients with unresectable hepatocellular carcinoma DRUG

The phase Ib portion of the trial explores the incidence of dose-limiting toxicity (DLT) in the quadruple therapeutic regimen. Three weeks after receiving Y90-SIRT, the patients are assigned to one of three dose exploration cohorts: (1) nivolumab 1 mg/kg IV every 3 weeks (Q3W) + ipilimumab 1 mg/kg IV Q3W for up to 4 cycles; (2) nivolumab 1 mg/kg IV Q3W + ipilimumab 2 mg/kg IV Q3W for up to 4 cycles; (3) nivolumab 1 mg/kg IV Q3W + ipilimumab 3 mg/kg IV Q3W for up to 4 cycles. After completion of ipilimumab administration, nivolumab is continued at 480 mg IV every 4 weeks (Q4W) until disease progression, unacceptable toxicity, withdrawal of informed consent, or a maximum treatment duration of two years. Lenvatinib is then administered after discontinuation of ipilimumab, in combination with nivolumab, at a dose of 8 mg (body weight \<60 kg) or 12 mg (body weight \>60 kg) orally once daily (PO QD), taken at a fixed time each day, with or without food.

Yttrium-90 microspheres in combination with nivolumab, ipilimumab, and lenvatinib

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• HCC confirmed as unresectable by imaging or histology, or patients who refuse surgery. Eligible for Y90-SIRT, with no evidence of extrahepatic disease on any available imaging. Lymph node involvement is permitted. The term "unresectable hepatocellular carcinoma" refers to a clinical state in which radical surgical resection is precluded because the tumor extent or an inadequate anticipated future liver remnant would prevent R0 removal, or because the procedural risk is prohibitively high, and where surgical intervention is not expected to yield a survival advantage over non-surgical therapies.
• Aged between 18 and 80 years at the time of enrollment
• Participants with Child-Pugh class A.
• Participants with an ECOG performance status of 0 or 1 at the time of enrollment
• Participants with a lung dose threshold of 30 Gy for yttrium-90 microspheres (each treatment dose ≤ 30 Gy), and an anticipated future liver remnant volume (FLRV) ≥ 30% of the total liver volume.
• Participants with one or more measurable lesions; for those with segmental or right anterior/posterior portal vein invasion (Vp1/Vp2), the disease is confined to a single lobe and suitable for Y90 microsphere treatment.
• No prior systemic therapy or transarterial radioembolization (Y90 glass microsphere TARE).
• No active autoimmune disease and no history of chronic or recurrent autoimmune disease.
• Adequate hematological, liver, and renal function as follows: (1) Absolute neutrophil count ≥ 1,500/mm³ (2) Hemoglobin level ≥ 9.0 g/dL (3) Platelet count ≥ 75,000/mm³ (4) Total bilirubin ≤ 1.5 × ULN (5) AST ≤ 2.5 × ULN (6) ALT ≤ 2.5 × ULN (7) International normalized ratio (INR) ≤ 1.25 (8) Albumin ≥ 31 g/L (9) 24-hour urine collection creatinine clearance (CL) \> 40 mL/min or calculated creatinine clearance (CL) \> 40 mL/min.
• Not pregnant and no intention to conceive before or during treatment.
• Written informed consent from the patient.
• Expected survival of at least 12 weeks.

You may not qualify if:

• Diffuse HCC or presence of vascular invasion or extrahepatic spread, with the following exceptions: invasion of segmental portal vein or hepatic vein.
• Patients with Child-Pugh class C cirrhosis.
• Any contraindication to hepatic arterial embolization: Known hepatic arterial reflux; known portosystemic shunt; coagulopathy (platelet count \< 50 × 109/L, INR \> 1.5); renal failure/insufficiency requiring hemodialysis or peritoneal dialysis; known severe arteriosclerosis; complete thrombosis or complete invasion of the main portal vein.
• History of heart disease: congestive heart failure \> New York Heart Association (NYHA) class II; active coronary artery disease (CAD) (myocardial infarction ≥ 6 months prior to study initiation is permitted); arrhythmias that are difficult to control with antiarrhythmic drugs or require a pacemaker (NCI-CTCAE v5.0 \> grade 2); uncontrolled hypertension; clinically significant gastrointestinal bleeding within 4 weeks prior to initiation of study drugs.
• Thrombotic or embolic events, such as cerebrovascular accident (including transient ischemic attack), deep vein thrombosis, or pulmonary embolism, occurring within 6 months prior to the first administration of study drug, except for segmental portal vein thrombosis.
• Receipt of systemic anticancer therapy, radiotherapy, endocrine therapy, immunotherapy, or other investigational drugs within 4 weeks prior to study initiation.
• Current or prior use of immunosuppressive drugs within 28 days before the first administration of nivolumab or ipilimumab. Exceptions to this criterion include: intranasal, inhaled, topical steroids or local steroid injections (e.g., intra-articular injection); physiological doses of systemic corticosteroids not exceeding 10 mg/day of prednisone or equivalent; steroids used for the prevention of allergic reactions (e.g., premedication for CT scan).
• Receipt of live attenuated vaccines within 30 days prior to the first administration of study drug (IP). Note: If the patient is enrolled, live vaccines should not be administered during the study drug treatment period and within 30 days after the last dose of the study drug.
• Major surgery within 4 weeks prior to study initiation, and the patient must have recovered from the effects of major surgery.
• Patients with a second primary malignancy, apart from adequately treated basal cell carcinoma of the skin or carcinoma in situ of the cervix, unless disease-free for more than 3 years.
• Uncontrolled comorbidities, including but not limited to persistent or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina, arrhythmia, interstitial lung disease, severe chronic gastrointestinal disease associated with diarrhea, or psychiatric/social conditions that limit compliance with study requirements, significantly increase the risk of adverse events, or impair the patient's ability to provide written informed consent.
• Active infections, including tuberculosis (clinical assessment including medical history, physical examination, and imaging, as well as tuberculosis testing according to local practice), hepatitis B (known positive HBV surface antigen \[HBsAg\]), and hepatitis C. Patients with past or resolved HBV infection (defined as presence of hepatitis B core antibody \[anti-HBc\] and absence of HBsAg) are eligible. Patients who are HCV antibody-positive are eligible only if HCV RNA measured by PCR is negative.
• History of allogeneic organ transplantation.
• Psychiatric disorders or altered mental status that interfere with understanding the informed consent process and/or compliance with the study protocol.
• Symptomatic brain metastases. If symptoms are present, imaging is required to confirm the absence of brain metastases.

Sponsors & Collaborators

• West China Hospital: lead

Study Sites (1)

Study Chair Liu Chang , West China Hospital

Chengdu, Sichuan, 610041, China

RECRUITING

Related Publications (17)

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• Jia Fan 2025 ESMO poster 1495

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Related Links

• CRIS

MeSH Terms

Interventions

Nivolumab; Ipilimumab; lenvatinib

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

Chang Liu, 医生

CONTACT

+86 189 8060 6382; drliuchang@wchscu.cn

Ruihong Dai, 医生

CONTACT

18715779637; 760173632@qq.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Doctor of Surgery

Study Record Dates

• First Submitted: February 27, 2026
• First Posted: March 19, 2026
• Study Start: February 1, 2026
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2028
• Last Updated: March 19, 2026

Record last verified: 2026-02

Locations

CN (1)