Phase III Study of Rilvegostomig in Combination withBevacizumab with or without Tremelimumab as First-lineTreatment of Hepatocellular Carcinoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AstraZeneca AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

18 Mar 2026 → ongoing

Decision date (initial)

2025-10-06

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-518210-81-00

ClinicalTrials.gov

NCT06921785

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacokinetic, Pharmacoeconomic, Therapy, Safety, Pharmacogenetic

To demonstrate the efficacy of rilvegostomig in combination with tremelimumab and bevacizumab (Arm A) relative to atezolizumab and bevacizumab (Arm C) by assessment of OS in participants with advanced HCC

Secondary objectives 7

1. To demonstrate the efficacy of Arm B relative to Arm C by assessment of OS in participants with advanced HCC
2. To further demonstrate the efficacy of Arm A relative to Arm C and Arm B relateive to Arm C in participants with advanced HCC
3. To demonstrate the efficacy of Arm A relative to Arm B in participants with advanced HCC
4. To demonstrate the efficacy of Arm A relative to Arm C in the population defined by PD-L1 expression subgroups
5. To demonstrate the efficacy of Arm B relative to Arm C in the population defined by PD-L1 expression subgroups
6. To investigate the immunogenicity of Arm A and Arm B
7. Occurrence of adverse events (AEs) and serious adverse events (SAEs)

Conditions and MedDRA coding

Advanced Hepatocellular Carcinoma

Study design 3 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared. AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment https://vivli.org/. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Locally advanced or metastatic and/or unresectable HCC
2. WHO/ECOG performance status of 0 or 1
3. BCLC stage B (that is not eligible for locoregional therapy) or stage C. Child-Pugh Score class A
4. At least one measurable target lesion
5. Co-infected with HBV and HCV are not eligible
6. Adequate organ and bone marrow function measured during the screening period
7. Must not have received prior systemic therapy for intermediate, advanced, or metastatic HCC.
8. Disease that is not amenable to curative surgical and/or locoregional therapies. Participants who have received approved adjuvant therapy (including immune checkpoint inhibitor treatment) must have a minimum interval of 6 months between the completion of such therapy and the documented diagnosis of recurrent or metastatic disease. 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 13

1. Any evidence of uncontrolled intercurrent diseases
2. Active or prior documented autoimmune or inflammatory disorders requiring chronic treatment with steroids or other immunosuppressive treatment
3. History of another primary malignancy
4. Persistent toxicities caused by previous anti-cancer therapy excluding alopecia, not yet improved to Grade ≤ 1 or baseline
5. 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.
6. History of active primary immunodeficiency or active infection
7. History of hepatic encephalopathy
8. 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
9. 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
10. Bleeding or other risks. HCC related - Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC.
11. Bleeding or other risks. HCC related - Central nervous system metastases or spinal cord compression (including asymptomatic and adequately treated disease)
12. Bleeding or other risks. HCC related - Prior treatment with anti-CTLA-4 and/or anti-TIGIT.
13. Bleeding or other risks. HCC related - 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall Survival (OS)

Secondary endpoints 1

1. PFS, ORR, DoR by BICR per RECIST v1.1

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Comparator 1

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AstraZeneca AB

Sponsor organisation

AstraZeneca AB

Address

-

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Public contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Locations

6 EU/EEA countries · 50 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 51 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications