Hepatocellular Carcinoma (HCC)Phase 2NCT07882056
SBRT Combined With Iparomlimab and Tuvonralimab (QL1706) and Bevacizumab for Hepatocellular Carcinoma
A Phase 2 study testing Stereotactic Body Radiotherapy, Bevacizumab and Iparomlimab and Tuvonralimab in people with Hepatocellular Carcinoma (HCC), run by Peking University Cancer Hospital & Institute at 1 site in China.
Trial summary
SBRT combined with dual PD-1/CTLA-4 blockade (iparomlimab and tuvonralimab, QL1706) and bevacizumab may provide complementary local and systemic antitumor activity in hepatocellular carcinoma (HCC). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatocellular Carcinoma (HCC)
- What is being tested?
- Stereotactic Body Radiotherapy, Bevacizumab and Iparomlimab and Tuvonralimab
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 1 siteChina
- Study dates
- 15 Oct 2026to Aug 2031
- Phase
- Phase 2
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age >= 18 years, male or female.
- Histologically or radiologically confirmed hepatocellular carcinoma.
- Barcelona Clinic Liver Cancer (BCLC) stage B or C.
- Inoperable disease, not a transplant candidate, and unsuitable for ablation or transarterial therapy, including locally advanced and oligometastatic disease. 4.1 Locally advanced: no extrahepatic metastasis; portal vein, hepatic vein, or inferior vena cava tumor thrombus permitted. 4.2 Oligometastatic: a limited number (<=5) of extrahepatic metastatic lesions (lymph node, visceral, bone, adrenal, or soft tissue; brain metastases excluded), with or without intrahepatic disease meeting the locally advanced definition. Vascular invasion is not counted in the lesion number, and lesions achieving complete response (per RECIST 1.1) after prior therapy are not counted.
- At least one measurable lesion per RECIST 1.1.
- All lesions can safely receive stereotactic body radiotherapy.
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- No prior systemic therapy, or progression or intolerance after first-line systemic therapy, with more than 3 weeks since the last dose.
- ECOG performance status 0-1 within 1 week before enrollment.
- Child-Pugh class A or B (score <=7).
- Hematology: hemoglobin >=90 g/L; white blood cell count >=3.0 x 10^9/L; absolute neutrophil count >=1.5 x 10^9/L; platelet count >=75 x 10^9/L.
- INR <=2.3, or prothrombin time exceeding the upper limit of normal by <=6 seconds.
- ALT and AST <=5 x upper limit of normal (ULN); alkaline phosphatase <=5 x ULN; total bilirubin <=3 x ULN; albumin >=28 g/L.
- Serum creatinine <=1.5 x ULN, or creatinine clearance >=50 mL/min calculated by the Cockcroft-Gault formula.
- Urine protein <2+ (patients with urine protein >=2+ may undergo 24-hour urine protein quantification and are eligible if the 24-hour urine protein is <1.0 g).
- Patients with active hepatitis B virus (HBV) infection: HBV-DNA <500 IU/mL (or <2500 copies/mL if only copy/mL is available) and willingness to receive antiviral therapy throughout the study; patients positive for hepatitis C virus (HCV) RNA must receive standard antiviral therapy, with hepatic enzyme elevation <=CTCAE grade 1.
- Women of childbearing potential (generally 15-49 years) must have a negative serum or urine pregnancy test within 14 days before enrollment and be willing to use adequate contraception during the study and for 8 weeks after the last dose of study drug; men must be surgically sterile or agree to adequate contraception during the study and for 8 weeks after the last dose.
- Voluntary participation with signed informed consent, good compliance, and willingness to undergo follow-up.
Who cannot join
- Age <18 years.
- ECOG performance status >=2.
- Poor liver function: Child-Pugh score >7, or hepatic enzymes, coagulation, bilirubin, or bone marrow function not meeting the enrollment criteria.
- Hepatic encephalopathy, massive ascites, or abdominal infection within 1 month.
- Brain metastases.
- Malignant pleural effusion.
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- Prior radiotherapy to any site requiring treatment in this study (risk of field overlap causing excessive irradiation of normal tissue).
- Prior selective internal radiation therapy or yttrium-90 hepatic arterial therapy.
- Tumor directly invading the stomach, duodenum, small intestine, or large intestine; or tumor within 3 mm of the spinal cord.
- Maximum diameter of any single lesion >15 cm.
- Sum of the maximum diameters of all intrahepatic lesions, or the maximum diameter of a single confluent lesion, >20 cm.
- More than 5 discrete intrahepatic HCC lesions.
- Normal liver volume <700 mL.
- Known history of allogeneic organ or hematopoietic stem cell transplantation, or planned transplantation.
- Known allergy to iparomlimab and tuvonralimab, bevacizumab, or drug excipients, or severe hypersensitivity to any other monoclonal antibody.
- Live attenuated vaccination within 4 weeks before the first dose or planned during the study.
- Severe active autoimmune disease.
- Any other malignancy, except adequately treated basal cell or squamous cell skin carcinoma or cervical carcinoma in situ.
- Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS).
- Within 6 months before enrollment: myocardial infarction, severe or unstable angina, NYHA class >=2 heart failure, poorly controlled arrhythmia, or symptomatic congestive heart failure.
- Coagulation abnormality with bleeding tendency, or currently receiving thrombolytic, anticoagulant, or antiplatelet therapy.
- Known hereditary or acquired bleeding or thrombotic tendency, such as hemophilia, coagulation disorders, or severe thrombocytopenia.
- Risk of gastrointestinal bleeding, including: (1) active peptic ulcer; (2) melena or hematemesis within 1 month; (3) gastroscopy showing ulcer or bleeding lesions, esophagogastric varices with red color signs (+), or variceal diameter >1 cm. Also: history of psychotropic drug abuse or drug addiction, or other severe medical or psychiatric illness, or laboratory abnormality that may increase study risk, confound results, or render the patient unsuitable in the investigator's judgment.
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
Beijing Cancer Hospital
Beijing, 100142
Weihu Wang, MD, +86 18810189122, zhengxuan54321@163.com
About this study
Official title: Effectiveness and Safety of Stereotactic Body Radiotherapy Combined With Iparomlimab and Tuvonralimab and Bevacizumab in Patients With Locally Advanced or Oligometastatic Hepatocellular Carcinoma: A Prospective, Single-Arm, Single-Center Study
SBRT combined with dual PD-1/CTLA-4 blockade (iparomlimab and tuvonralimab, QL1706) and bevacizumab may provide complementary local and systemic antitumor activity in hepatocellular carcinoma (HCC). This prospective, single-arm, single-center study evaluates the efficacy and safety of stereotactic body radiotherapy (SBRT) to all intra- and extrahepatic lesions combined with QL1706 (7.5 mg/kg intravenously on day 1 every 3 weeks) and bevacizumab (15 mg/kg intravenously on day 1 every 3 weeks) in patients with inoperable locally advanced or oligometastatic HCC (BCLC stage B or C). All lesions receive SBRT at 8 Gy in 3-5 fractions completed within 30 days; systemic therapy starts within 1 week before or after the start of radiotherapy and continues as maintenance for up to 2 years, until progression, death, or unacceptable toxicity. The primary endpoint is objective response rate per RECIST 1.1. Secondary endpoints include complete response, disease control rate, time to response, duration of response, local control, progression-free survival, time to progression, and overall survival per RECIST 1.1 and mRECIST, safety per CTCAE v6.0, and quality of life per EORTC QLQ-C30 and QLQ-HCC18. A total of 33 patients will be enrolled at Beijing Cancer Hospital.
Read the detailed description
Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer death worldwide. Immune checkpoint inhibition combined with anti-angiogenic therapy is the standard first-line systemic treatment for unresectable HCC, but outcomes remain suboptimal. Radiotherapy is not only an effective local treatment but also a potent immunomodulator; stereotactic body radiotherapy (SBRT) can induce immunogenic cell death, promote type I interferon and damage-associated molecular pattern release, and prime antitumor T-cell responses, providing a rationale for combining SBRT with dual PD-1/CTLA-4 blockade and anti-VEGF therapy. No prospective evidence currently exists for SBRT combined with dual immunotherapy plus anti-angiogenic therapy in unresectable HCC.
Objective: To evaluate the efficacy and safety of SBRT combined with iparomlimab and tuvonralimab (QL1706, a bifunctional PD-1/CTLA-4 antibody) and bevacizumab in patients with inoperable locally advanced or oligometastatic HCC.
Design: Prospective, single-arm, single-center, exploratory interventional study at Beijing Cancer Hospital. Enrollment period: 24 months; estimated 33 participants. Eligibility: adults (>=18 years) with imaging- or pathology-proven, inoperable BCLC stage B or C HCC unsuitable for surgery, ablation, or transarterial therapy, either locally advanced (portal/hepatic/inferior vena cava tumor thrombus permitted) or oligometastatic (up to 5 extrahepatic lesions); no prior systemic therapy or progression/intolerance after first-line therapy; ECOG 0-1; Child-Pugh A or B (score <=7); Child-Pugh class, laboratory thresholds, and the full inclusion and exclusion criteria are listed in the Eligibility module.
Interventions: All intra- and extrahepatic lesions receive SBRT with a prescription of 8 Gy x 3-5 fractions (fraction number determined by lesion location and proximity to organs at risk), one fraction per day or every other day on weekdays, with all treatment completed within 30 days and interfraction intervals of 24-72 hours; image-guided radiotherapy is used at every fraction. QL1706 7.5 mg/kg and bevacizumab 15 mg/kg are given intravenously on day 1 of each 21-day cycle, starting within 1 week before or after the start of SBRT; after the combined-treatment phase, both drugs continue as maintenance until 2 years of cumulative systemic treatment, disease progression, death, or unacceptable toxicity.
Outcome measures and statistical analysis: The outcome measures are listed in the Outcome Measures module; in brief, the primary endpoint is objective response rate per RECIST 1.1, with response assessed by investigators on the first imaging assessment 4-6 weeks after SBRT and every 12 weeks thereafter. Time-to-event endpoints are estimated with the Kaplan-Meier method. Efficacy is analyzed in all patients receiving at least one dose of study treatment or radiotherapy; safety (CTCAE v6.0) is analyzed in all patients receiving any study treatment. All analyses are two-sided with alpha = 0.05. Exploratory translational studies use blood (genetic sequencing, immune-related factors, plasma PD-1/PD-L1, T-cell receptor repertoire) and stool (metabolomics, metagenomics) specimens collected before the first dose, after completion of radiotherapy, and at progression.
- Conditions
- Hepatocellular Carcinoma (HCC)
- Being tested
- Stereotactic Body Radiotherapy, Bevacizumab, Iparomlimab and Tuvonralimab
- Keywords
- SBRT, bevacizumab, immunotherapy, oligometastatic
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Stereotactic Body RadiotherapyRadiation
SBRT to all intra- and extrahepatic lesions. Prescription dose 8 Gy x 3-5 fractions, with the fraction number determined by lesion location and proximity to organs at risk; one fraction per day or every other day on weekdays; interfraction interval 24-72 hours; the entire course completed within 30 days; image-guided radiotherapy at every fraction.
BevacizumabDrug
Bevacizumab injection. 15 mg/kg intravenous infusion on day 1 of each 21-day cycle, on the same schedule as QL1706, continued as maintenance until 2 years of cumulative treatment, disease progression, death, or unacceptable toxicity.
Iparomlimab and TuvonralimabDrug
QL1706 (commercial name Qibeian), a bifunctional anti-PD-1/CTLA-4 combination antibody. 7.5 mg/kg intravenous infusion on day 1 of each 21-day cycle, starting within 1 week before or after the start of SBRT and continued as maintenance until 2 years of cumulative treatment, disease progression, death, or unacceptable toxicity.
| Study group | Role | What they receive |
|---|---|---|
| SBRT + QL1706 + Bevacizumab | Experimental | All patients receive stereotactic body radiotherapy (SBRT) to all intra- and extrahepatic lesions (8 Gy x 3-5 fractions, completed within 30 days), plus iparomlimab and tuvonralimab (QL1706) 7.5 mg/kg and bevacizumab 15 mg/kg intravenously on day 1 of each 21-day cycle, starting within 1 week before or after the start of radiotherapy and continued as maintenance until 2 years of cumulative treatment, disease progression, death, or unacceptable toxicity. Receives: Radiation: Stereotactic Body Radiotherapy; Drug: Bevacizumab; Drug: Iparomlimab and Tuvonralimab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate per RECIST 1.1
Proportion of patients achieving complete response or partial response per RECIST 1.1, assessed by investigators.
Measured: From the first imaging assessment performed 4-6 weeks after completion of SBRT, repeated every 12 weeks until progression, death, or completion of 2-year follow-up
Secondary outcomes (13)
Complete Response (CR) per RECIST 1.1
Proportion of patients achieving complete response (disappearance of all target lesions) per RECIST 1.1, assessed by investigators.
Measured: From the first imaging assessment performed 4-6 weeks after completion of SBRT, repeated every 12 weeks until progression, death, or completion of 2-year follow-up
Disease Control Rate (DCR) per RECIST 1.1
Proportion of patients achieving complete response, partial response, or stable disease (CR + PR + SD) per RECIST 1.1, assessed by investigators.
Measured: From the first imaging assessment performed 4-6 weeks after completion of SBRT, repeated every 12 weeks until progression, death, or completion of 2-year follow-up
Time to Response (TOR)
Time from enrollment to the first documented tumor response per RECIST 1.1 and mRECIST.
Measured: From enrollment to the first documented response (RECIST 1.1 and mRECIST), up to 2 years
Duration of Response (DOR)
Time from first documented response until disease progression or death from any cause, per RECIST 1.1 and mRECIST.
Measured: From first documented response to disease progression or death from any cause, up to 2 years
Local Control (LC)
Time from enrollment to first progression within the high-dose irradiated region (within the 80% isodose line), per RECIST 1.1 and mRECIST.
Measured: From enrollment to first progression within the irradiated volume (within the 80% isodose line), assessed every 12 weeks, up to 2 years
Progression-Free Survival (PFS)
Time from enrollment to disease progression or death from any cause, per RECIST 1.1 and mRECIST.
Measured: From enrollment to disease progression or death from any cause, up to 2 years
Time to Progression (TTP)
Time from enrollment to disease progression, per RECIST 1.1 and mRECIST.
Measured: From enrollment to disease progression, up to 2 years
Overall Survival (OS)
Time from enrollment until death from any cause.
Measured: From enrollment to death from any cause, up to 2 years of follow-up
Incidence of Adverse Events
Incidence, severity (CTCAE v6.0), relatedness, and outcome of adverse events and serious adverse events, including incidence of grade 3 or higher events, treatment-related events, fatal events, and events leading to treatment discontinuation.
Measured: From first dose of study treatment until 30 days after the last dose for adverse events and serious adverse events; safety follow-up visit 6 weeks after the last dose
Composite of Quality of Life by EORTC QLQ-C30 and QLQ-HCC18
Quality of life assessed with the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30, version 3.0; 30 items) and its hepatocellular carcinoma-specific supplemental module (EORTC QLQ-HCC18; 18 items). All scale scores are transformed linearly to a range from 0 to 100; a higher score represents a better outcome for the global health status and functional scales, and a worse outcome for the symptom scales. Scores are calculated per the official EORTC scoring manual.
Measured: At baseline, every 1-2 weeks during radiotherapy, and at each treatment cycle until the end of treatment, up to 2 years
Objective Response Rate (ORR) per mRECIST
Proportion of patients achieving complete response or partial response (CR + PR) per modified RECIST (mRECIST), assessed by investigators.
Measured: From the first imaging assessment performed 4-6 weeks after completion of SBRT, repeated every 12 weeks until progression, death, or completion of 2-year follow-up
Complete Response (CR) per mRECIST
Proportion of patients achieving complete response per modified RECIST (mRECIST), assessed by investigators.
Measured: From the first imaging assessment performed 4-6 weeks after completion of SBRT, repeated every 12 weeks until progression, death, or completion of 2-year follow-up
Disease Control Rate (DCR) per mRECIST
Proportion of patients achieving complete response, partial response, or stable disease (CR + PR + SD) per modified RECIST (mRECIST), assessed by investigators.
Measured: From the first imaging assessment performed 4-6 weeks after completion of SBRT, repeated every 12 weeks until progression, death, or completion of 2-year follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Oct 2026
- Study start15 Oct 2026 (estimated)
- Primary completionAug 2030 (estimated)
- Study completionAug 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatocellular Carcinoma (HCC)Studies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 33 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Peking University Cancer Hospital & Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Weihu Wang, MD, Principal investigator, Peking University Cancer Hospital & Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07882056
- Sponsor's protocol ID
- PKUCH-HCC-SBRT01
- Status last verified
- Oct 2026
- First submitted
- 12 Oct 2026
- Last updated
- 20 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided