Unresectable Hepatocellular CarcinomaPhase 1/2NCT07482059
A Multicenter Clinical Study of Combined Therapy for Unresectable Hepatocellular Carcinoma
A Phase 1/2 study testing ttrium-90 microspheres in combination with nivolumab, ipilimumab, and lenvatinib in patients with unresectable hepatocellular carcinoma in people with Unresectable Hepatocellular Carcinoma, run by West China Hospital at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Unresectable Hepatocellular Carcinoma
- What is being tested?
- ttrium-90 microspheres in combination with nivolumab, ipilimumab, and lenvatinib in patients with unresectable hepatocellular carcinoma
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 1 siteChina
- Study dates
- Feb 2026to 30 Jun 2028
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- If the patient is co-infected with hepatitis B virus (HBV) or hepatitis C virus (HCV), the following criteria must be met: HBV or HCV viral levels should be monitored during study participation. Patients with detectable hepatitis B surface antigen (HBsAg) or HBV DNA should have HBV DNA < 100 IU/ml and be managed according to local treatment guidelines. Most patients with advanced HCC and HCV have not received treatment for HCV infection. However, if antiviral therapy has been completed prior to the first administration of study drugs, these patients are considered eligible for inclusion.
- 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.
Who cannot join
- 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.
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- 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.
- Pregnant or breastfeeding women.
- Immunocompromised patients, such as those known to be serologically positive for human immunodeficiency virus (HIV).
- Active or previously documented autoimmune or inflammatory diseases (including inflammatory bowel disease [such as colitis or Crohn's disease], diverticulitis [excluding diverticulosis], systemic lupus erythematosus, sarcoidosis, or Wegener's granulomatosis [granulomatosis with polyangiitis], Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, among others).
- Known allergy or hypersensitivity to any study drug or its components.
- Currently participating in or previously participated in a study involving an investigational drug, or use of an investigational device within 4 weeks prior to the first administration of study treatment.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Study Chair Liu Chang , West China Hospital
Chengdu, Sichuan, 610041
Chang Liu, 医生, +86 189 8060 6382, drliuchang@wchscu.cn
Ruihong Dai, 医生, +86 18715779637, 760173632@qq.com
About this study
Official title: A Multicenter Phase Ib/II Clinical Study on the Safety and Efficacy of Selective Internal Radiation Therapy (SIRT) With Yttrium-90 Microspheres in Combination With Nivolumab, Ipilimumab, and Lenvatinib in Patients With Unresectable Hepatocellular Carcinoma
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
- Being tested
- ttrium-90 microspheres in combination with nivolumab, ipilimumab, and lenvatinib in patients with unresectable hepatocellular carcinoma
- Keywords
- unresectable hepatocellular carcinoma, Yttrium-90 microsphere selective internal radiation therapy (Y90-SIRT), nivolumab, pilimumab, lenvatinib, phase Ib/II study
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ttrium-90 microspheres in combination with nivolumab, ipilimumab, and lenvatinib in patients with unresectable hepatocellular carcinomaDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: ttrium-90 microspheres in combination with nivolumab, ipilimumab, and lenvatinib in patients with unresectable hepatocellular carcinoma |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of dose-limiting toxicity (DLT) of the quadruple regimen (Y90-SIRT plus nivolumab, ipilimumab, lenvatinib)
Measured: Up to 4 treatment cycles (each cycle is 3 weeks)
Objective response rate (ORR) assessed by both iRECIST and mRECIST criteria
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Mar 2026
- Study startFeb 2026 (estimated)
- Primary completion30 Jun 2026 (estimated)
- Study completion30 Jun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (17)Papers the sponsor has linked to this study.
- Other trials for Unresectable Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by West China HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 33 participants (estimated)
Sponsor and investigators
- Lead sponsor
- West China Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, LiuChang, West China Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07482059
- Sponsor's protocol ID
- 20252727
- Status last verified
- Feb 2026
- First submitted
- 27 Feb 2026
- Last updated
- 19 Mar 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Zhu HD, Fan WJ, Zhao C, Wang S, Li YL, Jin ZC, Zhang ZW, Guo JH, Cheng HT, Zhang Q, Lu J, Zeng YY, Lv WF, Xu H, Shao HB, Xu WG, Zhao XY, Gu SZ, Lin HL, Zheng WH, Piao LZ, Song YS, Zhao JB, Wang YC, Hou ZG, Sun Y, Guan N, Huang M, Yang WZ, Ji JS, Teng GJ. Transarterial Chemoembolization Combined With Camrelizumab and Rivoceranib for Unresectable Hepatocellular Carcinoma (CHANCE2005/CARES-005): A Randomized Phase II Trial. J Clin Oncol. 2026 Apr 10;44(11):959-969. doi: 10.1200/JCO-25-01796. Epub 2026 Feb 24.
PubMed 41734362Feng Y, Roy A, Masson E, Chen TT, Humphrey R, Weber JS. Exposure-response relationships of the efficacy and safety of ipilimumab in patients with advanced melanoma. Clin Cancer Res. 2013 Jul 15;19(14):3977-86. doi: 10.1158/1078-0432.CCR-12-3243. Epub 2013 Jun 5.
PubMed 23741070Twyman-Saint Victor C, Rech AJ, Maity A, Rengan R, Pauken KE, Stelekati E, Benci JL, Xu B, Dada H, Odorizzi PM, Herati RS, Mansfield KD, Patsch D, Amaravadi RK, Schuchter LM, Ishwaran H, Mick R, Pryma DA, Xu X, Feldman MD, Gangadhar TC, Hahn SM, Wherry EJ, Vonderheide RH, Minn AJ. Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer. Nature. 2015 Apr 16;520(7547):373-7. doi: 10.1038/nature14292. Epub 2015 Mar 9.
PubMed 25754329Kudo et al. HCC. Study 117. Phase 1b of lenvatinib + NIVO in unresectable HCC. ASCOGI 2020. Poster
Agrawal et al. Journal for ImmunoTherapy of Cancer (2016) 4:72
Zhan C, Ruohoniemi D, Shanbhogue KP, Wei J, Welling TH, Gu P, Park JS, Dagher NN, Taslakian B, Hickey RM. Safety of Combined Yttrium-90 Radioembolization and Immune Checkpoint Inhibitor Immunotherapy for Hepatocellular Carcinoma. J Vasc Interv Radiol. 2020 Jan;31(1):25-34. doi: 10.1016/j.jvir.2019.05.023. Epub 2019 Aug 14.
PubMed 31422022Mejait A, Roux C, Soret M, Larrey E, Wagner M, Bijot JC, Lussey-Lepoutre C, Thabut D, Goumard C, Maksud P, Allaire M. Enhanced therapeutic outcomes with atezolizumab-bevacizumab and SIRT combination compared to SIRT alone in unresectable HCC: A promising approach for improved survival. Clin Res Hepatol Gastroenterol. 2024 Feb;48(2):102282. doi: 10.1016/j.clinre.2024.102282. Epub 2024 Jan 6.
PubMed 38191073DiFederico,A.,Rizzo,A.,Carloni,R.,DeGiglio,A.,Bruno,R.,Ricci,D.,&Brandi,G.(2022).Atezolizumab-bevacizumabplusY-90TAREforthetreatmentofhepatocellularcarcinoma:preclinicalrationaleandongoingclinicaltrials.Expertopiniononinvestigationaldrugs,
Craciun L, de Wind R, Demetter P, Lucidi V, Bohlok A, Michiels S, Bouazza F, Vouche M, Tancredi I, Verset G, Garaud S, Naveaux C, Galdon MG, Gallo KW, Hendlisz A, Derijckere ID, Flamen P, Larsimont D, Donckier V. Retrospective analysis of the immunogenic effects of intra-arterial locoregional therapies in hepatocellular carcinoma: a rationale for combining selective internal radiation therapy (SIRT) and immunotherapy. BMC Cancer. 2020 Feb 19;20(1):135. doi: 10.1186/s12885-020-6613-1.
PubMed 32075608Grass GD, Krishna N, Kim S. The immune mechanisms of abscopal effect in radiation therapy. Curr Probl Cancer. 2016 Jan-Feb;40(1):10-24. doi: 10.1016/j.currproblcancer.2015.10.003. Epub 2015 Nov 21.
PubMed 26612692Formenti SC, Rudqvist NP, Golden E, Cooper B, Wennerberg E, Lhuillier C, Vanpouille-Box C, Friedman K, Ferrari de Andrade L, Wucherpfennig KW, Heguy A, Imai N, Gnjatic S, Emerson RO, Zhou XK, Zhang T, Chachoua A, Demaria S. Radiotherapy induces responses of lung cancer to CTLA-4 blockade. Nat Med. 2018 Dec;24(12):1845-1851. doi: 10.1038/s41591-018-0232-2. Epub 2018 Nov 5.
PubMed 30397353Jia Fan 2025 ESMO poster 1495
Yau T, Galle PR, Decaens T, Sangro B, Qin S, da Fonseca LG, Karachiwala H, Blanc JF, Park JW, Gane E, Pinter M, Pena AM, Ikeda M, Tai D, Santoro A, Pizarro G, Chiu CF, Schenker M, He A, Chon HJ, Wojcik-Tomaszewska J, Verset G, Wang QQ, Stromko C, Neely J, Singh P, Jimenez Exposito MJ, Kudo M; CheckMate 9DW investigators. Nivolumab plus ipilimumab versus lenvatinib or sorafenib as first-line treatment for unresectable hepatocellular carcinoma (CheckMate 9DW): an open-label, randomised, phase 3 trial. Lancet. 2025 May 24;405(10492):1851-1864. doi: 10.1016/S0140-6736(25)00403-9. Epub 2025 May 8.
PubMed 40349714Lu W, Zhang T, Xia F, Huang X, Gao F. Transarterial radioembolization versus chemoembolization for hepatocellular carcinoma: a meta-analysis. Front Oncol. 2025 Jan 17;14:1511210. doi: 10.3389/fonc.2024.1511210. eCollection 2024.
PubMed 39896190中国医师协会介入医师分会临床诊疗指南专委会, 中国研究型医院学会肝胆胰外科专业委员会. 钇-90微球选择性内放射治疗肝脏恶性肿瘤规范化操作专家共识（2024版）[J] . 中华医学杂志, 2024, 104(7) : 486-498.
Study at a glance
From the registry record, last updated by the sponsor on 19 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter Phase Ib/II Clinical Study on the Safety and Efficacy of Selective Internal Radiation Therapy (SIRT) With Yttrium-90 Microspheres in Combination With Nivolumab, Ipilimumab, and Lenvatinib in Patients With Unresectable Hepatocellular Carcinoma
- ClinicalTrials.gov ID
- NCT07482059
- Acronym / sponsor ID
- 20252727
- Conditions
- Unresectable Hepatocellular Carcinoma
- Keywords
- unresectable hepatocellular carcinoma, Yttrium-90 microsphere selective internal radiation therapy (Y90-SIRT), nivolumab, pilimumab, lenvatinib, phase Ib/II study
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 33 participants (estimated)
- Lead sponsor
- West China HospitalUniversity, hospital or other
- Study start
- Feb 2026 (estimated)
- Primary completion
- 30 Jun 2026 (estimated)
- Study completion
- 30 Jun 2028 (estimated)
- First posted
- 19 Mar 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Yttrium-90 microspheres in combination with nivolumab, ipilimumab, and lenvatinib | Experimental | Drug: ttrium-90 microspheres in combination with nivolumab, ipilimumab, and lenvatinib in patients with unresectable hepatocellular carcinomaThe 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. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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.
Key exclusion criteria (20 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ttrium-90 microspheres in combination with nivolumab, ipilimumab, and lenvatinib in patients with unresectable hepatocellular carcinomaThe 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 | Yttrium-90 microspheres in combination with nivolumab, ipilimumab, and lenvatinib |
Primary outcome
Incidence of dose-limiting toxicity (DLT) of the quadruple regimen (Y90-SIRT plus nivolumab, ipilimumab, lenvatinib)
Time frame: Up to 4 treatment cycles (each cycle is 3 weeks)
Objective response rate (ORR) assessed by both iRECIST and mRECIST criteria
Time frame: 24 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Mar 2026.
- Background: PubMed 41734362Zhu HD, Fan WJ, Zhao C, Wang S, Li YL, Jin ZC, Zhang ZW, Guo JH, Cheng HT, Zhang Q, Lu J, Zeng YY, Lv WF, Xu H, Shao HB, Xu WG, Zhao XY, Gu SZ, Lin HL, Zheng WH, Piao LZ, Song YS, Zhao JB, Wang YC, Hou ZG, Sun Y, Guan N, Huang M, Yang WZ, Ji JS, Teng GJ. Transarterial Chemoembolization Combined With Camrelizumab and Rivoceranib for Unresectable Hepatocellular Carcinoma (CHANCE2005/CARES-005): A Randomized Phase II Trial. J Clin Oncol. 2026 Apr 10;44(11):959-969. doi: 10.1200/JCO-25-01796. Epub 2026 Feb 24.
- Background: PubMed 23741070Feng Y, Roy A, Masson E, Chen TT, Humphrey R, Weber JS. Exposure-response relationships of the efficacy and safety of ipilimumab in patients with advanced melanoma. Clin Cancer Res. 2013 Jul 15;19(14):3977-86. doi: 10.1158/1078-0432.CCR-12-3243. Epub 2013 Jun 5.
- Background: PubMed 25754329Twyman-Saint Victor C, Rech AJ, Maity A, Rengan R, Pauken KE, Stelekati E, Benci JL, Xu B, Dada H, Odorizzi PM, Herati RS, Mansfield KD, Patsch D, Amaravadi RK, Schuchter LM, Ishwaran H, Mick R, Pryma DA, Xu X, Feldman MD, Gangadhar TC, Hahn SM, Wherry EJ, Vonderheide RH, Minn AJ. Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer. Nature. 2015 Apr 16;520(7547):373-7. doi: 10.1038/nature14292. Epub 2015 Mar 9.
- BackgroundKudo et al. HCC. Study 117. Phase 1b of lenvatinib + NIVO in unresectable HCC. ASCOGI 2020. Poster
- BackgroundAgrawal et al. Journal for ImmunoTherapy of Cancer (2016) 4:72
- Background: PubMed 31422022Zhan C, Ruohoniemi D, Shanbhogue KP, Wei J, Welling TH, Gu P, Park JS, Dagher NN, Taslakian B, Hickey RM. Safety of Combined Yttrium-90 Radioembolization and Immune Checkpoint Inhibitor Immunotherapy for Hepatocellular Carcinoma. J Vasc Interv Radiol. 2020 Jan;31(1):25-34. doi: 10.1016/j.jvir.2019.05.023. Epub 2019 Aug 14.
- Background: PubMed 38191073Mejait A, Roux C, Soret M, Larrey E, Wagner M, Bijot JC, Lussey-Lepoutre C, Thabut D, Goumard C, Maksud P, Allaire M. Enhanced therapeutic outcomes with atezolizumab-bevacizumab and SIRT combination compared to SIRT alone in unresectable HCC: A promising approach for improved survival. Clin Res Hepatol Gastroenterol. 2024 Feb;48(2):102282. doi: 10.1016/j.clinre.2024.102282. Epub 2024 Jan 6.
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- Background: PubMed 32075608Craciun L, de Wind R, Demetter P, Lucidi V, Bohlok A, Michiels S, Bouazza F, Vouche M, Tancredi I, Verset G, Garaud S, Naveaux C, Galdon MG, Gallo KW, Hendlisz A, Derijckere ID, Flamen P, Larsimont D, Donckier V. Retrospective analysis of the immunogenic effects of intra-arterial locoregional therapies in hepatocellular carcinoma: a rationale for combining selective internal radiation therapy (SIRT) and immunotherapy. BMC Cancer. 2020 Feb 19;20(1):135. doi: 10.1186/s12885-020-6613-1.
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- BackgroundJia Fan 2025 ESMO poster 1495
- CRISLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing ttrium-90 microspheres in combination with nivolumab, ipilimumab, and lenvatinib in patients with unresectable hepatocellular carcinoma in people with Unresectable Hepatocellular Carcinoma, run by West China Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 19 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Chang Liu, 医生 (+86 189 8060 6382, drliuchang@wchscu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of dose-limiting toxicity (DLT) of the quadruple regimen (Y90-SIRT plus nivolumab, ipilimumab, lenvatinib) (time frame: Up to 4 treatment cycles (each cycle is 3 weeks)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07482059, which also lists 17 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Mar 2026.