Recruiting NCT06921785

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

Phase III Interventional Hepatocellular Carcinoma

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied: The protocol lists: Tremelimumab, Rilvegostomig, Bevacizumab, Atezolizumab.
Who it may be relevant to: Registry conditions: Hepatocellular Carcinoma. Basic parameters: from 18 years · All.
What needs checking: Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place: United States, Australia, Brazil, Canada, China +15
Next step: Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Official title

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

Overview

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.

Interventions

Drug Tremelimumab
IV therapy
Drug Rilvegostomig
IV therapy
Drug Bevacizumab
IV therapy
Drug Atezolizumab
IV therapy

Primary outcome measures

To demonstrate the efficacy of Arm A relative to Arm C by assessment of OS in participants with advanced HCC [Time frame: Up to approximately 6 years]

Secondary outcome measures (12)

To demonstrate the efficacy of Arm B relative to Arm C by assessment of OS in participants with advanced HCC [Time frame: Up to approximately 6 years]
To further demonstrate the efficacy of Arm A relative to Arm C and Arm B relative to Arm C in participants with advanced HCC [Time frame: Up to approximately 6 years]
To further demonstrate the efficacy of Arm A relative to Arm C and Arm B relative to Arm C in participants with advanced HCC [Time frame: Up to approximately 6 years]
To further demonstrate the efficacy of Arm A relative to Arm C and Arm B relative to Arm C in participants with advanced HCC [Time frame: Up to approximately 6 years]
To demonstrate the efficacy of Arm A relative to Arm B in participants with advanced HCC [Time frame: Up to approximately 6 years]
To demonstrate the efficacy of Arm A relative to Arm B in participants with advanced HCC [Time frame: Up to approximately 6 years]
To demonstrate the efficacy of Arm A relative to Arm B in participants with advanced HCC [Time frame: Up to approximately 6 years]
To demonstrate the efficacy of Arm A relative to Arm B in participants with advanced HCC [Time frame: Up to approximately 6 years]
To demonstrate the efficacy of Arm A relative to Arm C in the population defined by PD-L1 expression subgroups [Time frame: Up to approximately 6 years]
To demonstrate the efficacy of Arm A relative to Arm C in the population defined by PD-L1 expression subgroups [Time frame: Up to approximately 6 years]
To demonstrate the efficacy of Arm A relative to Arm C in the population defined by PD-L1 expression subgroups [Time frame: Up to approximately 6 years]
To demonstrate the efficacy of Arm B relative to Arm C in the population defined by PD-L1 expression subgroups [Time frame: Up to approximately 6 years]

Eligibility 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation: Randomized
Model: Parallel assignment
Masking: Single blind
Primary purpose: Treatment

Study locations

United States · 35 centers

Research Site — Phoenix
Research Site — Tucson
Research Site — Los Angeles
Research Site — Palo Alto
Research Site — New Haven
Research Site — Newark
Research Site — Jacksonville
Research Site — Atlanta
… and 27 more centers

China · 35 centers

Research Site — Beijing
Research Site — Beijing
Research Site — Beijing
Research Site — Changchun
Research Site — Changsha
Research Site — Chengdu
Research Site — Chifeng
Research Site — Chongqing
… and 27 more centers

Japan · 30 centers