Phase III Study of Rilvegostomig in Combination With Bevacizumab With or Without Tremelimumab as First-line Treatment of Hepatocellular Carcinoma (ARTEMIDE-HCC01)

AstraZeneca

Status and phase: Enrolling; Phase 3

Conditions: Hepatocellular Carcinoma

Treatments: Drug: Bevacizumab; Drug: Rilvegostomig; Drug: Atezolizumab; Drug: Tremelimumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT06921785

D7029C00001

Details and patient eligibility

About

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

Full 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.

Enrollment: 1,220 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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1,220 participants in 3 patient groups

Arm A

Experimental group

Description:

Tremelimumab , rilvegostomig and bevacizumab

Treatment:

Drug: Tremelimumab

Drug: Rilvegostomig

Drug: Bevacizumab

Arm B

Experimental group

Description:

Rilvegostomig, and bevacizumab

Treatment:

Drug: Rilvegostomig

Drug: Bevacizumab

Arm C

Active Comparator group

Description:

Atezolizumab, and bevacizumab

Treatment:

Drug: Atezolizumab

Drug: Bevacizumab