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Not yet recruitingNCT07882056Updated Oct 20, 2026

SBRT Combined With Iparomlimab and Tuvonralimab (QL1706) and Bevacizumab for Hepatocellular Carcinoma

A Phase 2 interventional study of Stereotactic Body Radiotherapy and Bevacizumab in Hepatocellular Carcinoma (HCC), sponsored by Peking University Cancer Hospital & Institute. Not yet recruiting at 1 site in China. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-10-20.

Sponsored by Peking University Cancer Hospital & Institute · Phase 2, Interventional, and Treatment

Updated Oct 20, 2026Newly registeredGo to Updates ↓
Phase
Phase 2
Study type
Interventional
Enrollment
33
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study 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). 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.

02

Conditions studied

  • Hepatocellular Carcinoma (HCC)

Keywords

  • SBRT
  • bevacizumab
  • immunotherapy
  • oligometastatic
03

In context

Carcinoma, Hepatocellular

3,249 studies on the registry are indexed under Carcinoma, Hepatocellular; 974 are open to participants now.

This study's planned enrollment of 33 is below the median of 55 across 2,347 interventional studies indexed under Carcinoma, Hepatocellular.

Browse Carcinoma, Hepatocellular studies →

Lead sponsor

Peking University Cancer Hospital & Institute is the lead sponsor of 266 studies on the registry; 128 are open to participants now.

Browse Peking University Cancer Hospital & Institute studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  1. Age >= 18 years, male or female.
  2. Histologically or radiologically confirmed hepatocellular carcinoma.
  3. Barcelona Clinic Liver Cancer (BCLC) stage B or C.
  4. 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.
  5. At least one measurable lesion per RECIST 1.1.
  6. All lesions can safely receive stereotactic body radiotherapy.
  7. No prior systemic therapy, or progression or intolerance after first-line systemic therapy, with more than 3 weeks since the last dose.
  8. ECOG performance status 0-1 within 1 week before enrollment.
  9. Child-Pugh class A or B (score \<=7).
  10. 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.
  11. INR \<=2.3, or prothrombin time exceeding the upper limit of normal by \<=6 seconds.
  12. ALT and AST \<=5 x upper limit of normal (ULN); alkaline phosphatase \<=5 x ULN; total bilirubin \<=3 x ULN; albumin >=28 g/L.
  13. Serum creatinine \<=1.5 x ULN, or creatinine clearance >=50 mL/min calculated by the Cockcroft-Gault formula.
  14. 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).
  15. 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.
  16. 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.
  17. Voluntary participation with signed informed consent, good compliance, and willingness to undergo follow-up.

Exclusion criteria

Exclusion Criteria:

  1. Age \<18 years.
  2. ECOG performance status >=2.
  3. Poor liver function: Child-Pugh score >7, or hepatic enzymes, coagulation, bilirubin, or bone marrow function not meeting the enrollment criteria.
  4. Hepatic encephalopathy, massive ascites, or abdominal infection within 1 month.
  5. Brain metastases.
  6. Malignant pleural effusion.
  7. Prior radiotherapy to any site requiring treatment in this study (risk of field overlap causing excessive irradiation of normal tissue).
  8. Prior selective internal radiation therapy or yttrium-90 hepatic arterial therapy.
  9. Tumor directly invading the stomach, duodenum, small intestine, or large intestine; or tumor within 3 mm of the spinal cord.
  10. Maximum diameter of any single lesion >15 cm.
  11. Sum of the maximum diameters of all intrahepatic lesions, or the maximum diameter of a single confluent lesion, >20 cm.
  12. More than 5 discrete intrahepatic HCC lesions.
  13. Normal liver volume \<700 mL.
  14. Known history of allogeneic organ or hematopoietic stem cell transplantation, or planned transplantation.
  15. Known allergy to iparomlimab and tuvonralimab, bevacizumab, or drug excipients, or severe hypersensitivity to any other monoclonal antibody.
  16. Live attenuated vaccination within 4 weeks before the first dose or planned during the study.
  17. Severe active autoimmune disease.
  18. Any other malignancy, except adequately treated basal cell or squamous cell skin carcinoma or cervical carcinoma in situ.
  19. Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS).
  20. Within 6 months before enrollment: myocardial infarction, severe or unstable angina, NYHA class >=2 heart failure, poorly controlled arrhythmia, or symptomatic congestive heart failure.
  21. Coagulation abnormality with bleeding tendency, or currently receiving thrombolytic, anticoagulant, or antiplatelet therapy.
  22. Known hereditary or acquired bleeding or thrombotic tendency, such as hemophilia, coagulation disorders, or severe thrombocytopenia.
  23. 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.
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
33 participants (estimated)

Study arms

  • Experimental
    SBRT + QL1706 + Bevacizumab

    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.

    Radiation: Stereotactic Body Radiotherapy · Drug: Bevacizumab · Drug: Iparomlimab and Tuvonralimab

Interventions

  • RadiationStereotactic Body Radiotherapy

    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.

  • DrugBevacizumab

    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.

  • DrugIparomlimab and Tuvonralimab

    Drug pages: Iparomlimab · Tuvonralimab

    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.

06

What researchers measure

Primary outcomes

  1. Objective Response Rate per RECIST 1.1

    Proportion of patients achieving complete response or partial response per RECIST 1.1, assessed by investigators.

    Time frame: 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

  1. 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.

    Time frame: 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

  2. 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.

    Time frame: 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

  3. Time to Response (TOR)

    Time from enrollment to the first documented tumor response per RECIST 1.1 and mRECIST.

    Time frame: From enrollment to the first documented response (RECIST 1.1 and mRECIST), up to 2 years

  4. Duration of Response (DOR)

    Time from first documented response until disease progression or death from any cause, per RECIST 1.1 and mRECIST.

    Time frame: From first documented response to disease progression or death from any cause, up to 2 years

  5. 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.

    Time frame: From enrollment to first progression within the irradiated volume (within the 80% isodose line), assessed every 12 weeks, up to 2 years

  6. Progression-Free Survival (PFS)

    Time from enrollment to disease progression or death from any cause, per RECIST 1.1 and mRECIST.

    Time frame: From enrollment to disease progression or death from any cause, up to 2 years

  7. Time to Progression (TTP)

    Time from enrollment to disease progression, per RECIST 1.1 and mRECIST.

    Time frame: From enrollment to disease progression, up to 2 years

  8. Overall Survival (OS)

    Time from enrollment until death from any cause.

    Time frame: From enrollment to death from any cause, up to 2 years of follow-up

  9. 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.

    Time frame: 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

  10. 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.

    Time frame: At baseline, every 1-2 weeks during radiotherapy, and at each treatment cycle until the end of treatment, up to 2 years

  11. Objective Response Rate (ORR) per mRECIST

    Proportion of patients achieving complete response or partial response (CR + PR) per modified RECIST (mRECIST), assessed by investigators.

    Time frame: 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

  12. Complete Response (CR) per mRECIST

    Proportion of patients achieving complete response per modified RECIST (mRECIST), assessed by investigators.

    Time frame: 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

  13. 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.

    Time frame: 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

07

Study locations

1 site
  • Beijing Cancer Hospital
    Beijing, 100142, China
08

References and documents

Individual participant data

Plan to share: Undecided

No publications or documents are linked to this record.

09

Timeline

1 registry update since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reachedSimilar studies: half by the dot; the band is the middle halfHalf of similar studies reached it by the dot; the band is the middle half, from a quarter to three quarters

Start is estimated for Oct 2026; primary completion for Aug 2030, 46 months later.

Of 328 non-industry phase 2 interventional studies under Carcinoma, Hepatocellular, half reached primary completion within 49 months of starting (the median), counting those still running; a quarter within 34 and three quarters within 74. This study's planned 46 months is close to that.

Counting every sponsor, half of 404 studies reached it within 44 months; a quarter within 31 and three quarters within 70.

How these figures are worked out, and which studies are left out of them.

Registered
Oct 12, 2026
First posted
Oct 20, 2026
StartEst.
Oct 15, 2026
Primary completionEst.
Aug 2030
CompletionEst.
Aug 2031
Last update
Oct 20, 2026
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
Registered
First appeared on the registry. No changes since
Oct 20, 2026
Show all 1 update
  1. Oct 20, 2026
    First appeared on the registry

From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗

10

Registry details

Key details

Study ID
NCT07882056
Lead sponsor
Peking University Cancer Hospital & Institute
Responsible party
Sponsor
First posted
Oct 20, 2026
Start date
Oct 15, 2026 (estimated)
Primary completion
Aug 2030 (estimated)
Completion
Aug 2031 (estimated)
Last update
Oct 20, 2026

Study contacts

Xuan Zheng, MD
Contact
zhengxuan54321@163.com
+86 18810189122
Weihu Wang, MD
principal investigator · Peking University Cancer Hospital & Institute

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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