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

Phase 2

Recruiting

• Conditions: Hepatocellular Carcinoma; Biliary Tract Cancer
• Interventions: Drug: Volrustomig; Drug: Rilvegostomig; Drug: Lenvatinib; Drug: Bevacizumab; Drug: Gemcitabine; Drug: Cisplatin

• Registration Number: NCT05775159
• Lead Sponsor: AstraZeneca

Brief Summary

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.

Detailed Description

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 60 evaluable participants with advanced BTC who have not received previous treatment for advanced/metastatic disease.

Study Timeline

• Study First Submitted: 2023-03-02
• Study First Submitted QC: 2023-03-17
• Study First Posted: 2023-03-20
• Study Start: 2023-04-24
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-19
• Last Update Posted: 2024-11-21
• Primary Completion: 2025-12-31
• Study Completion: 2027-01-26

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 260

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Cohort 1B	Volrustomig	Volrustomig combination with bevacizumab
Cohort 1C	Lenvatinib	Volrustomig combination with lenvatinib
Cohort 2A	Rilvegostomig	Rilvegostomig combination with Gemcitabine and Cisplatin
Cohort 2A	Cisplatin	Rilvegostomig combination with Gemcitabine and Cisplatin
Cohort 2B	Volrustomig	Volrustomig combination with Gemcitabine and Cisplatin
Cohort 1A	Volrustomig	Volrustomig monotherapy
Cohort 1B	Bevacizumab	Volrustomig combination with bevacizumab
Cohort 1C	Volrustomig	Volrustomig combination with lenvatinib
Cohort 1D	Volrustomig	Volrustomig combination with rilvegostomig and bevacizumab
Cohort 1D	Bevacizumab	Volrustomig combination with rilvegostomig and bevacizumab
Cohort 1D	Rilvegostomig	Volrustomig combination with rilvegostomig and bevacizumab
Cohort 1E	Rilvegostomig	Rilvegostomig combination with bevacizumab
Cohort 2A	Gemcitabine	Rilvegostomig combination with Gemcitabine and Cisplatin
Cohort 2B	Gemcitabine	Volrustomig combination with Gemcitabine and Cisplatin
Cohort 2B	Cisplatin	Volrustomig combination with Gemcitabine and Cisplatin
Cohort 1E	Bevacizumab	Rilvegostomig combination with bevacizumab

Primary Outcome Measures

Name	Time	Method
The number of participants with adverse events/serious adverse events	Through study completion, an average of 2 years	Number of participants with adverse events and with serious adverse events including abnormal clinical observations, abnormal Electrocardiogram (ECG) parameters, abnormal laboratory assessments and abnormal vital signs that changed from baseline.
Progression free survival (PFS)	Through study completion, an average of 2 years	PFS is defined as the time from the start of studyintervention until progression per RECIST 1.1 as assessed by the Investigator at the local site or death due to any cause in the absence of progression, whichever occurs first. (For BTC sub-study 2)
Objective response rate (ORR)	Through study completion, an average of 2 years	ORR is defined as the proportion of participants who have a confirmed CR (complete response) or confirmed PR (partial response), determined by the Investigator at local site per RECIST 1.1 (For HCC sub-study 1)

Secondary Outcome Measures

Name	Time	Method
Duration Of Response (DOR)	Through study completion, an average of 2 years	DoR is defined as the time from the date of first documented confirmed response until date of documented progression per RECIST 1.1 by the Investigator at local site or death due to any cause in the absence of disease progression, whichever occurs first.
Progression free survival (PFS)	Through study completion, an average of 2 years	PFS is defined as the time from the start of study intervention until progression per RECIST 1.1 as assessed by the Investigator at the local site or death due to any cause in the absence of progression, whichever occurs first.
Pharmacokinetics of novel immunomodulators: Time to maximum plasma concentration of the study drug (T-max)	From the first dose of study intervention, at predefined intervals throughout the administration of novel immunomodulators ( approx 2 years )	Time to maximum observed plasma concentration of the study drug
lmmunogenicity of novel immunomodulators	From the first dose of study intervention, at predefined intervals throughout the administration of novel immunomodulators ( approx 2 years)	The number and percentage of participants who develop ADAs.
Disease Control Rate (DCR)	At 12 and 24 weeks	DCR at 12 and 24 weeks is defined as the percentage of participants who have a Complete response (CR) or Partial response (PR) in the first 13 and 25 weeks or who have Stable disease (SD) for at least 11 and 23 weeks after the date of first dose respectively, per RECIST 1.1 as assessed by the investigator at local site and derived from the raw tumour data.
Overall Survival (OS)	Through study completion, an average of 2 years	OS is defined as the time from the start of study intervention until the date of death due to any cause, whichever occurs first.
Anti Drug Antibody (ADA)	Through study completion, an average of 2 years	Incidences of ADAs against novel immunomodulators in serum.
Pharmacokinetics of novel immunomodulators: Maximum plasma concentration of the study drug (Cmax)	From the first dose of study intervention, at predefined intervals throughout the administration of novel immunomodulators ( approx 2 years )	Maximum observed plasma concentration of the study drug
Objective response rate (ORR)	Through study completion, an average of 2 years	ORR is defined as the proportion of participants who have a confirmed CR (complete response) or confirmed PR (partial response), determined by the Investigator at local site per RECIST 1.1

Trial Locations

Locations (1)

Research Site; 🇬🇧 Manchester, United Kingdom