Bevacizumab followed by atezolizumab versus both together for advanced hepatocellular carcinoma with MASLD

The Efficacy of Sequential Treatment With Bevacizumab Combined With Atezolizumab in Advanced Liver Cancer With MASLD Background: a Dual Arm, Multicenter, Randomized Controlled Study

This test will see if giving bevacizumab first and then atezolizumab works better than giving both at the same time for adults with advanced hepatocellular carcinoma and metabolic-associated steatotic liver disease (MASLD).

Quick facts

• Phase: Phase2; Phase3
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Eastern Hepatobiliary Surgery Hospital (Academic / other)
• Drugs / interventions: immunotherapy, prednisone, bevacizumab, atezolizumab
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT07285850 on ClinicalTrials.gov

What this trial studies

This randomized phase 2/3 study will enroll 20 patients with advanced, unresectable hepatocellular carcinoma and moderate-to-severe MASLD and assign them to either sequential or concurrent bevacizumab plus atezolizumab for up to six months with follow-up. Primary clinical endpoints include objective response rate, progression-free survival, disease control rate, and overall survival, with safety monitored by CTCAE v5.0. Serial liver biopsies and biomarker testing will analyze tumor microenvironment changes (including T-cell calcium signaling, VEGFA expression, and other immune factors) before and after treatment. The study will also explore how baseline metabolic measures (blood lipids, insulin resistance) relate to treatment response.

Who should consider this trial

Good fit: Adults (≥18 years) with advanced unresectable HCC (BCLC C or D), moderate-to-severe fatty liver by CAP or MRI, ECOG 0–1, at least one measurable lesion, adequate organ function, and expected survival ≥3 months are ideal candidates.

Not a fit: Patients with poor hepatic reserve (Child–Pugh B/C), unmeasurable disease, active contraindications to immunotherapy or anti-VEGF therapy, or major comorbidities are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, this approach could identify a better timing strategy for combining bevacizumab and atezolizumab that improves tumor response and survival for MASLD-associated HCC patients.

How similar studies have performed: Atezolizumab plus bevacizumab has shown benefit in HCC broadly, but the question of sequential versus concurrent dosing specifically in MASLD-associated HCC is novel and largely untested.

Eligibility criteria

Eligibility Criteria Inclusion Criteria

* Age ≥ 18 years old (gender not limited)
* ECOG performance status of 0-1
* Preoperative imaging diagnosis of advanced hepatocellular carcinoma (BCLC stage C or D, unsuitable for surgery)
* Ultrasound or MRI indicating moderate to severe fatty liver (Fibroscan CAP \> 268 dB/m or MR fat score \> 10%)
* Willing to use contraceptive measures during the trial period
* Expected survival time ≥ 3 months
* At least one measurable lesion (per RECIST 1.1) that has not been irradiated
* Organ function levels (within 7 days before first study medication) must meet the following:
* Hematopoietic function: ANC ≥ 1.5×10⁹/L, PLT ≥ 100×10⁹/L, Hb ≥ 90 g/L, no transfusion within 14 days
* Liver function: TBIL ≤ 1.5×ULN, AST/ALT/ALP ≤ 2.5×ULN, serum creatinine ≤ 1.5×ULN, CrCl ≥ 50 mL/min, ALB ≥ 30 g/L, Child-Pugh A
* Coagulation function: INR and APTT ≤ 1.5×ULN or within therapeutic range if on anticoagulants
* Renal function: urinary protein ≤ 1+ (or ≤1 g/24h if \>1+)
* Cardiac function: ECG normal or clinically insignificant, LVEF \> 50%
* Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to first dosing
* Men and women of reproductive potential must use effective contraception during and for 12 months after treatment
* Participants must voluntarily provide informed consent and have good compliance

Exclusion Criteria

* Excessive alcohol consumption (weekly ethanol intake: males \< 210 g, females \< 140 g)
* Tumor lesions previously treated with targeted therapy, immunotherapy, TACE, or radiotherapy
* Pregnant or breastfeeding women, or positive pregnancy test at baseline
* Central nervous system metastases diagnosed by CT, MRI, or PET-CT
* Participation in another clinical drug or therapy trial within 4 weeks before first study dose
* Major surgery within 4 weeks prior to first study dose, or incomplete recovery from surgery
* Radiotherapy within 2 weeks before first study dose
* History or presence of primary immunodeficiency or active autoimmune disease
* History of organ transplantation or hematopoietic stem cell transplantation
* Current use of immunosuppressants or corticosteroids (\>10 mg/day prednisone or equivalent) within 2 weeks
* Positive for HIV antibody or Treponema pallidum antibody, or active hepatitis B/C infection
* Allergy to recombinant humanized PD-1 monoclonal antibody, VEGF monoclonal antibody, or components
* Symptomatic pleural effusion, pericardial effusion, or ascites requiring clinical intervention
* Severe cardiovascular disease within 12 months (e.g., CAD, CHF ≥ II, arrhythmias, MI)
* Events within 6 months before first dose (e.g., DVT, PE, MI, PCI, ACS, CABG, stroke, TIA, embolism)
* History of GI surgery, obstruction, bleeding, dysfunction, or malabsorption affecting drug absorption
* Severe uncontrolled infection or comorbidity, or moderate/severe renal impairment
* Active pulmonary disease (interstitial pneumonia, COPD, asthma, tuberculosis history)
* Abnormal coagulation (INR \> 2.0, PT \> 16 s), bleeding tendency, or thrombolytic/anticoagulant therapy (except prophylaxis)
* Significant bleeding within 3 months (e.g., hemoptysis ≥ 2.5 mL, GI bleeding, varices, ulcers, vasculitis)
* Known hereditary/acquired bleeding or thrombotic disorders (e.g., hemophilia, thrombocytopenia)
* History of substance abuse or mental disorders affecting compliance
* Use of warfarin or coumarin derivatives within 14 days before or during treatment
* Other severe acute/chronic conditions increasing risk or confounding results
* Poor compliance or other conditions deemed unsuitable for trial participation

Where this trial is running

Shanghai, Shanghai Municipality

• Eastern Hepatobiliary Surgery Hospital — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Study coordinator: Hao Shen, M.D.

Conditions HCC - Hepatocellular Carcinoma; MASH; HCC; immunotherapy