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Rilvegostomig plus bevacizumab, with or without tremelimumab, versus atezolizumab plus bevacizumab for advanced liver cancer

A Phase III, Randomised, Open-label, Sponsor-blinded, Multicentre Study of Rilvegostomig in Combination With Bevacizumab With or Without Tremelimumab as First-line Treatment in Patients With Advanced Hepatocellular Carcinoma

PHASE3 · AstraZeneca · NCT06921785

This trial tests whether rilvegostomig combined with bevacizumab, with or without tremelimumab, works better than atezolizumab plus bevacizumab as first-line treatment for people with advanced hepatocellular carcinoma who are not candidates for curative or locoregional therapy.

Quick facts

PhasePHASE3
Study typeInterventional
Enrollment1220 (estimated)
Ages18 Years and up
SexAll
SponsorAstraZeneca (industry)
Drugs / interventionsbevacizumab, tremelimumab, atezolizumab
Locations217 sites (Phoenix, Arizona and 216 other locations)
Trial IDNCT06921785 on ClinicalTrials.gov

What this trial studies

This is a global, phase III, randomized, open-label, three-arm study with a single-arm safety lead-in to check tolerability of the rilvegostomig combination before randomization. Participants with locally advanced, unresectable, or metastatic hepatocellular carcinoma who have not received prior systemic therapy will be enrolled. The randomized period compares rilvegostomig plus bevacizumab with or without tremelimumab against the standard combination of atezolizumab plus bevacizumab. Efficacy and safety outcomes will be collected across multiple centers to determine whether the new combinations provide improved clinical benefit.

Who should consider this trial

Good fit: Ideal candidates are adults with locally advanced, unresectable, or metastatic HCC (BCLC B not eligible for locoregional therapy or BCLC C), ECOG 0–1, Child-Pugh A, at least one measurable lesion, no prior systemic therapy for advanced HCC, and controlled active HBV or HCV infections as required by protocol.

Not a fit: Patients with decompensated liver disease (Child-Pugh B or C), uncontrolled HBV or HCV, ECOG performance status >1, prior systemic therapy for advanced HCC, or those eligible for curative or locoregional therapies are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, the combinations with rilvegostomig could provide a new first-line option that improves tumor control or survival while maintaining acceptable tolerability.

How similar studies have performed: Atezolizumab plus bevacizumab has previously shown a first-line survival benefit in advanced HCC and other immunotherapy-plus-anti-VEGF combinations have been successful, but rilvegostomig-containing regimens are novel and still unproven in this setting.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* Locally advanced or metastatic and/or unresectable HCC
* WHO/ECOG performance status of 0 or 1
* BCLC stage B (that is not eligible for locoregional therapy) or stage C.
* Child-Pugh Score class A
* At least one measurable target lesion
* Participants with active HBV infection must receive antiviral therapy for a minimum of 14 days prior to randomization to show evidence of HBV stabilization or signs of viral response.
* Participants with active HCV infection must be well controlled. Participants co-infected with HBV and HCV are not eligible.
* Adequate organ and bone marrow function measured during the screening period.
* Adequate organ and bone marrow function measured during the screening period
* Must not have received prior systemic therapy for intermediate, advanced, or metastatic HCC.
* Disease that is not amenable to curative surgical and/or locoregional therapies. For participants who received locoregional therapy for HCC, locoregional therapy must have been completed ≥ 28 days prior to the baseline scan for the current study.

Exclusion Criteria:

Medical condition

* Any evidence of uncontrolled intercurrent diseases
* Active or prior documented autoimmune or inflammatory disorders requiring chronic treatment with steroids or other immunosuppressive treatment
* History of another primary malignancy
* Persistent toxicities caused by previous anti-cancer therapy excluding alopecia, not yet improved to Grade ≤ 1 or baseline.
* Clinically meaningful ascites, pleural effusion, or pericardial effusion requiring non-pharmacologic intervention to maintain symptomatic control within 6 months prior to the first scheduled dose.
* History of active primary immunodeficiency or active infection
* History of hepatic encephalopathy
* Current or recent (within 10 days of first dose of study treatment) use of aspirin (≥ 325 mg/day) or treatment with dipyridamole, ticlopidine, clopidogrel, and cilostazol
* Current or recent (within 10 days prior to study treatment start) use of full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic (as opposed to prophylactic) purposes is ineligible
* History of significant bleeding disorders, vasculitis, or a significant bleeding episode from the GI tract within 6 months prior to study randomization.
* Participants with untreated or incompletely treated varices with bleeding or high-risk (red wale signs or other high-risk factors) for bleeding.

HCC related

* Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC.
* Central nervous system metastases or spinal cord compression (including asymptomatic and adequately treated disease)
* Prior treatment with anti-CTLA-4 and/or anti-TIGIT.
* Radiotherapy within 28 days and abdominal/ pelvic radiotherapy within 60 days prior to initiation of study treatment, except palliative radiotherapy to bone lesions within 7 days prior to initiation of study treatment

Where this trial is running

Phoenix, Arizona and 216 other locations

+167 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.

View on ClinicalTrials.gov →

Conditions: Hepatocellular Carcinoma

Last reviewed 2026-05-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.