This is a Phase III, randomised, open-label, sponsor-blinded, 3-arm, multicentre, global study assessing the efficacy and safety of rilvegostomig in combination with bevacizumab with or without tremelimumab compared to atezolizumab in combination with bevacizumab. This study will be conducted in participants with advanced HCC who are not amenable to curative therapy or locoregional therapy

The purpose of this study is to assess the efficacy and tolerability of rilvegostomig in combination with bevacizumab with or without tremelimumab as first-line treatment in participants with advanced HCC. The study comprises 2 parts - a safety lead-in and a randomised period. Prior to the start of the randomised period of the study, a single-arm safety lead-in period will be applied to evaluate the safety and tolerability of rilvegostomig in combination with bevacizumab and tremelimumab.

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

Qualified researchers can request access to anonymized individualpatient-level data from AstraZeneca group of companies sponsoredclinical trials via the request portal Vivli.org. All requests will be evaluatedas per the AZ disclosure commitment:https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.Yes, indicates that AZ are accepting requests for IPD, but this does notmean all requests will be shared.

AstraZeneca will meet or exceed data availability as per the commitmentsmade to the EFPIA PhRMA Data Sharing Principles. For details of ourtimelines, please refer to our disclosure commitment athttps://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

When a request has been approved AstraZeneca will provide access to theanonymized individual patient-level data via secure research environmentVivli.org. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

The study will be conducted "Sponsor-blinded", Sponsor personnel directly involved in the study conduct will not have access to efficacy data aggregated by intervention arm prior to study unbinding.