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
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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
Primary outcome measure(s)
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.
Trial sites (219)
Facility
City
Region
Status
Research Site
Phoenix
Arizona
Recruiting
Research Site
Tucson
Arizona
Recruiting
Research Site
Los Angeles
California
Recruiting
Research Site
Palo Alto
California
Recruiting
Research Site
New Haven
Connecticut
Recruiting
Research Site
Newark
Delaware
Recruiting
Research Site
Jacksonville
Florida
Recruiting
Research Site
Orlando
Florida
Not Yet Recruiting
Research Site
Atlanta
Georgia
Recruiting
Research Site
Atlanta
Georgia
Withdrawn
Research Site
Honolulu
Hawaii
Withdrawn
Research Site
Chicago
Illinois
Recruiting
Research Site
Indianapolis
Indiana
Not Yet Recruiting
Research Site
Shreveport
Louisiana
Not Yet Recruiting
Research Site
Detroit
Michigan
Recruiting
Research Site
Grand Rapids
Michigan
Recruiting
Research Site
Rochester
Minnesota
Recruiting
Research Site
St Louis
Missouri
Not Yet Recruiting
Research Site
New Brunswick
New Jersey
Recruiting
Research Site
New York
New York
Recruiting
Research Site
New York
New York
Recruiting
Research Site
New York
New York
Not Yet Recruiting
Research Site
Cleveland
Ohio
Withdrawn
Research Site
Oklahoma City
Oklahoma
Not Yet Recruiting
Research Site
Philadelphia
Pennsylvania
Not Yet Recruiting
Research Site
Pittsburgh
Pennsylvania
Recruiting
Research Site
Amarillo
Texas
Recruiting
Research Site
Austin
Texas
Recruiting
Research Site
Dallas
Texas
Withdrawn
Research Site
Houston
Texas
Recruiting
Research Site
San Antonio
Texas
Recruiting
Research Site
Tyler
Texas
Recruiting
Research Site
Arlington
Virginia
Recruiting
Research Site
Salem
Virginia
Recruiting
Research Site
Seattle
Washington
Recruiting
Research Site
Milwaukee
Wisconsin
Recruiting
Research Site
Auchenflower
Australia
Recruiting
Research Site
Camperdown
Australia
Recruiting
Research Site
Clayton
Australia
Not Yet Recruiting
Research Site
Heidelberg
Australia
Recruiting
+ 179 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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