Hepatocellular Carcinoma
Conditions
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.
Interventions
DRUGTremelimumab
IV therapy
DRUGRilvegostomig
IV therapy
DRUGBevacizumab
IV therapy
DRUGAtezolizumab
IV therapy
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
The study will be conducted "Sponsor-blinded", Sponsor personnel directly involved in the study conduct will not have access to efficacy data aggregated by intervention arm prior to study unbinding.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To demonstrate the efficacy of Arm B 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. |
| To further demonstrate the efficacy of Arm A relative to Arm C and Arm B relative to Arm C in participants with advanced HCC | Up to approximately 6 years | PFS according to RECIST 1.1 |
| To demonstrate the efficacy of Arm A relative to Arm B in participants with advanced HCC | Up to approximately 6 years | OS |
| To demonstrate the efficacy of Arm A relative to Arm C in the population defined by PD-L1 expression subgroups | Up to approximately 6 years | Association of PD-L1 expression level with: • OS |
| To demonstrate the efficacy of Arm B relative to Arm C in the population defined by PD-L1 expression subgroups | Up to approximately 6 years | Association of PD-L1 expression level with: OS |
| To investigate the immunogenicity of Arm A and Arm B | Up to approximately 6 years | Presence of ADAs for tremelimumab and rilvegostomig |
| Occurrence of adverse events (AEs) and serious adverse events (SAEs) | Up to approximately 6 years | Occurrence of AEs and SAEs will be graded according to the revised NCI CTCAE v5.0. |
Countries
Australia, Brazil, Canada, China, France, Germany, Hong Kong, India, Italy, Japan, Netherlands, Poland, South Korea, Spain, Taiwan, Thailand, Turkey (Türkiye), United Kingdom, United States, Vietnam
Contacts
CONTACTAstraZeneca Clinical Study Information Center
Outcome results
None listed