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
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
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