Clinical trial NCT06921785: Phase III Study of Rilvegostomig in Combination With Bevacizumab With or Without Tremelimumab as First-line Treatment of Hepatocellular Carcinoma
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Hepatocellular Carcinoma
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2025-04-10
Enrollment: 1220
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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
* 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

Primary outcomes:
measure: To demonstrate the efficacy of Arm A relative to Arm C by assessment of OS in participants with advanced HCC
timeFrame: Up to approximately 6 years
Secondary outcomes:
measure: To demonstrate the efficacy of Arm B relative to Arm C by assessment of OS in participants with advanced HCC
timeFrame: Up to approximately 6 years
measure: To further demonstrate the efficacy of Arm A relative to Arm C and Arm B relateive to Arm C in participants with advanced HCC
timeFrame: Up to approximately 6 years
measure: To further demonstrate the efficacy of Arm A relative to Arm C and Arm B relateive to Arm C in participants with advanced HCC
timeFrame: Up to approximately 6 years
measure: To demonstrate the efficacy of Arm A relative to Arm B in participants with advanced HCC
timeFrame: Up to approximately 6 years
measure: To demonstrate the efficacy of Arm A relative to Arm B in participants with advanced HCC
timeFrame: Up to approximately 6 years
measure: To demonstrate the efficacy of Arm A relative to Arm B in participants with advanced HCC
timeFrame: Up to approximately 6 years
measure: To demonstrate the efficacy of Arm A relative to Arm B in participants with advanced HCC
timeFrame: Up to approximately 6 years
measure: To demonstrate the efficacy of Arm A relative to Arm C in the population defined by PD-L1 expression subgroups
timeFrame: Up to approximately 6 years
measure: To demonstrate the efficacy of Arm A relative to Arm C in the population defined by PD-L1 expression subgroups
timeFrame: Up to approximately 6 years
measure: To demonstrate the efficacy of Arm A relative to Arm C in the population defined by PD-L1 expression subgroups
timeFrame: Up to approximately 6 years
measure: To demonstrate the efficacy of Arm A relative to Arm C in the population defined by PD-L1 expression subgroups
timeFrame: Up to approximately 6 years
measure: To demonstrate the efficacy of Arm B relative to Arm C in the population defined by PD-L1 expression subgroups
timeFrame: Up to approximately 6 years
measure: To demonstrate the efficacy of Arm B relative to Arm C in the population defined by PD-L1 expression subgroups
timeFrame: Up to approximately 6 years
measure: To demonstrate the efficacy of Arm B relative to Arm C in the population defined by PD-L1 expression subgroups
timeFrame: Up to approximately 6 years
measure: To demonstrate the efficacy of Arm B relative to Arm C in the population defined by PD-L1 expression subgroups
timeFrame: Up to approximately 6 years
measure: To investigate the immunogenicity of Arm A and Arm B
timeFrame: Up to approximately 6 years
measure: Occurrence of adverse events (AEs) and serious adverse events (SAEs)
timeFrame: Up to approximately 6 years
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Research Site
state: Arizona
city: Palo Alto
country: United States
facility: Research Site
state: California
city: Jacksonville
country: United States
facility: Research Site
state: Florida
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Grand Rapids
country: United States
facility: Research Site
state: Michigan
city: Rochester
country: United States
facility: Research Site
state: Minnesota
city: New Brunswick
country: United States
facility: Research Site
state: New Jersey
city: Oklahoma City
country: United States
facility: Research Site
state: Oklahoma
city: Arlington
country: United States
facility: Research Site
state: Virginia
city: Milwaukee
country: United States
facility: Research Site
state: Wisconsin
city: Porto Alegre
country: Brazil
facility: Research Site
city: Sao Paulo
country: Brazil
facility: Research Site
city: Vitória
country: Brazil
facility: Research Site
city: Halifax
country: Canada
facility: Research Site
state: Nova Scotia
city: Barrie
country: Canada
facility: Research Site
state: Ontario
city: Cambridge
country: Canada
facility: Research Site
state: Ontario
city: Ottawa
country: Canada
facility: Research Site
state: Ontario
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Montréal
country: Canada
facility: Research Site
state: Quebec
city: Québec
country: Canada
facility: Research Site
state: Quebec
city: Beijing
country: China
facility: Research Site
city: Changchun
country: China
facility: Research Site
city: Chengdu
country: China
facility: Research Site
city: Deyang
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Lishui
country: China
facility: Research Site
city: Luoyang
country: China
facility: Research Site
city: Nanchang
country: China
facility: Research Site
city: Nanchang
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Wenzhou
country: China
facility: Research Site
city: Clichy Cedex
country: France
facility: Research Site
city: Lyon Cedex
country: France
facility: Research Site
city: Nantes Cedex 1
country: France
facility: Research Site
city: Nice
country: France
facility: Research Site
city: Pessac Cedex
country: France
facility: Research Site
city: Rennes
country: France
facility: Research Site
city: Toulouse
country: France
facility: Research Site
city: Aachen
country: Germany
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Bonn
country: Germany
facility: Research Site
city: Dortmund
country: Germany
facility: Research Site
city: Dresden
country: Germany
facility: Research Site
city: Essen
country: Germany
facility: Research Site
city: Frankfurt
country: Germany
facility: Research Site
city: Frankfurt
country: Germany
facility: Research Site
city: Göttingen
country: Germany
facility: Research Site
city: Hamburg
country: Germany
facility: Research Site
city: Hannover
country: Germany
facility: Research Site
city: Leipzig
country: Germany
facility: Research Site
city: Lübeck
country: Germany
facility: Research Site
city: Magdeburg
country: Germany
facility: Research Site
city: Moers
country: Germany
facility: Research Site
city: München
country: Germany
facility: Research Site
city: Regensburg
country: Germany
facility: Research Site
city: Ulm
country: Germany
facility: Research Site
city: Hong Kong
country: Hong Kong
facility: Research Site
city: Hong Kong
country: Hong Kong
facility: Research Site
city: Pisa
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Chiba-shi
country: Japan
facility: Research Site
city: Kashiwa
country: Japan
facility: Research Site
city: Kyoto-shi
country: Japan
facility: Research Site
city: Morioka-shi
country: Japan
facility: Research Site
city: Musashino-shi
country: Japan
facility: Research Site
city: Osakasayama-shi
country: Japan
facility: Research Site
city: Tokyo
country: Japan
facility: Research Site
city: Yokohama-shi
country: Japan
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Santander
country: Spain
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taoyuan
country: Taiwan
facility: Research Site
city: Altındağ
country: Turkey
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Erzurum
country: Turkey
facility: Research Site
city: Istanbul
country: Turkey
facility: Research Site
city: Izmir
country: Turkey
facility: Research Site
city: Hanoi
country: Vietnam
facility: Research Site
city: Ho Chi Minh City
country: Vietnam
facility: Research Site
city: Ho Chi Minh
country: Vietnam
facility: Research Site
Study officials:
References: