Study of Novel Immunomodulators as Monotherapy and in Combination With Anticancer Agents in Participants With Advanced Hepatobiliary Cancer

A Phase II, Open-Label, Multi-Drug, Multi-Center, Master Protocol to Evaluate the Efficacy and Safety of Novel Immunomodulators as Monotherapy and in Combination With Anticancer Agents in Participants With Advanced Hepatobiliary Cancer (GEMINI-Hepatobiliary)

GEMINI-Hepatobiliary study will assess the efficacy, safety and tolerability of novel immunomodulators alone and in combination with other anticancer drugs in participants with specified advanced solid tumors.

This Phase II, open-label, uncontrolled, multicentre study evaluating the preliminary efficacy and safety of Volrustomig or Rilvegostomig as monotherapy (MONO) and/or in combination with anticancer agents (COMBO) in participants with advanced hepatobiliary cancer (e.g., HCC, BTC, etc.).

This study has a modular design with independent substudies. In Substudy 1, Volrustomig and Rilvegostomig will be evaluated as monotherapy and/or in combination with other anticancer drugs in approximately 200 evaluable participants with advanced HCC.

In Substudy 2, the efficacy and safety of Rilvegostomig or Volrustomig plus gemcitabine and cisplatin are investigated in approximately 90 evaluable participants with advanced BTC who have not received previous treatment for advanced/metastatic disease.

Inclusion Criteria:

• Age ≥18 years at the time of signing the ICF.
• Provision of a signed and dated written ICF.
• Confirmed locally advanced or metastatic solid tumor specified in substudy based on histopathology.
• Adequate organ and bone marrow function.
• At least 1 measurable not previously irradiated lesion per RECIST 1.1
• Life expectancy of at least 12 weeks at the time of screening.
• Willing and able to provide an adequate tumor sample.

Exclusion Criteria:

• History of allogeneic organ transplantation.
• Active or prior documented autoimmune or inflammatory disorders.
• Uncontrolled intercurrent illness.
• History of another primary malignancy, leptomeningeal carcinomatosis, and active primary immunodeficiency.
• Active infection, brain metastases or spinal cord compression.
• Participants co-infected with HBV and hepatitis D virus (HDV).
• Previous treatment in the present study.
• For substudy 1, history of hepatic encephalopathy within 12 months prior to treatment allocation.