Phase III Study of Rilvegostomig in Combination With Bevacizumab With or Without Tremelimumab as First-line Treatment of Hepatocellular Carcinoma

Phase 3

Recruiting

• Conditions: Hepatocellular Carcinoma
• Interventions: Drug: Tremelimumab; Drug: Rilvegostomig; Drug: Atezolizumab; Drug: Bevacizumab

• Registration Number: NCT06921785
• Lead Sponsor: AstraZeneca

Brief Summary

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

Detailed Description

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.

Study Timeline

• Study First Submitted: 2025-03-26
• Study First Submitted QC: 2025-04-03
• Study First Posted: 2025-04-10
• Study Start: 2025-05-06
• Status Verified: 2025-08
• Last Update Submitted: 2025-08-28
• Last Update Posted: 2025-08-29
• Primary Completion: 2029-03-16
• Study Completion: 2030-03-14

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 1220

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
• co-infected with HBV and HCV are not eligible
• 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

Bleeding or other risks

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A	Tremelimumab	Tremelimumab , rilvegostomig and bevacizumab
Arm A	Rilvegostomig	Tremelimumab , rilvegostomig and bevacizumab
Arm A	Bevacizumab	Tremelimumab , rilvegostomig and bevacizumab
Arm B	Rilvegostomig	Rilvegostomig, and bevacizumab
Arm B	Bevacizumab	Rilvegostomig, and bevacizumab
Arm C	Bevacizumab	Atezolizumab, and bevacizumab
Arm C	Atezolizumab	Atezolizumab, and bevacizumab

Primary Outcome Measures

Name	Time	Method
To demonstrate the efficacy of Arm A relative to Arm C by assessment of OS in participants with advanced HCC	Up to approximately 6 years	OS is defined as the time from randomisation until the date of death due to any cause.

Secondary Outcome Measures

Name	Time	Method
To demonstrate the efficacy of Arm A relative to Arm B in participants with advanced HCC	Up to approximately 6 years	DoR
To further demonstrate the efficacy of Arm A relative to Arm C and Arm B relateive to Arm C in participants with advanced HCC	Up to approximately 6 years	ORR according to RECIST 1.1
To demonstrate the efficacy of Arm B relative to Arm C by assessment of OS in participants with advanced HCC	Up to approximately 6 years	OS is defined as the time from randomisation until the date of death due to any cause.
To demonstrate the efficacy of Arm A relative to Arm C in the population defined by PD-L1 expression subgroups	Up to approximately 6 years	Association of PD-L1 expression level with: •DoR per RECIST 1.1
To investigate the immunogenicity of Arm A and Arm B	Up to approximately 6 years	Presence of ADAs for tremelimumab and rilvegostomig
To demonstrate the efficacy of Arm B relative to Arm C in the population defined by PD-L1 expression subgroups	Up to approximately 6 years	Association of PD-L1 expression level with: DoR per RECIST 1.1
Occurrence of adverse events (AEs) and serious adverse events (SAEs)	Up to approximately 6 years	Occurrence of AEs and SAEs will be graded according to the revised NCI CTCAE v5.0.

Trial Locations

Locations (1)

Research Site; 🇻🇳 Ho Chi Minh City, Vietnam