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

April 11, 2024 updated by: AstraZeneca

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

260

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
      • Beijing, China, 100050
        • Recruiting
        • Research Site
      • Beijing, China, 100142
        • Recruiting
        • Research Site
      • Beijing, China, 101100
        • Recruiting
        • Research Site
      • Chengdu, China, 610000
        • Recruiting
        • Research Site
      • Chengdu, China, 610041
        • Recruiting
        • Research Site
      • Chongqing, China, 400030
        • Recruiting
        • Research Site
      • Fuzhou, China, 350007
        • Recruiting
        • Research Site
      • Guangzhou, China, 510060
        • Not yet recruiting
        • Research Site
      • Guangzhou, China, 510515
        • Recruiting
        • Research Site
      • Harbin, China, 150081
        • Recruiting
        • Research Site
      • Hefei, China, 230601
        • Not yet recruiting
        • Research Site
      • Hefei, China, 230001
        • Not yet recruiting
        • Research Site
      • Hefei, China, 230022
        • Recruiting
        • Research Site
      • Nanchang, China, 330006
        • Recruiting
        • Research Site
      • Nanning, China, 530021
        • Recruiting
        • Research Site
      • Shandong, China
        • Not yet recruiting
        • Research Site
      • Shanghai, China, 200032
        • Recruiting
        • Research Site
      • Xi'an, China, 710038
        • Not yet recruiting
        • Research Site
      • Zhengzhou, China, 450008
        • Withdrawn
        • Research Site
  • Hong Kong
      • Hong Kong, Hong Kong, 150001
        • Recruiting
        • Research Site
      • Shatin, Hong Kong, 00000
        • Recruiting
        • Research Site
  • Italy
      • Firenze, Italy, 50134
        • Recruiting
        • Research Site
      • Milano, Italy, 20132
        • Recruiting
        • Research Site
      • Napoli, Italy, 80131
        • Recruiting
        • Research Site
      • Rozzano, Italy, 20089
        • Recruiting
        • Research Site
  • Japan
      • Chuo-ku, Japan, 104-0045
        • Recruiting
        • Research Site
      • Kashiwa, Japan, 277-8577
        • Recruiting
        • Research Site
      • Yokohama-shi, Japan, 241-8515
        • Recruiting
        • Research Site
  • Korea, Republic of
      • Seongnam-Si, Korea, Republic of, 463-712
        • Recruiting
        • Research Site
      • Seoul, Korea, Republic of, 03722
        • Recruiting
        • Research Site
      • Seoul, Korea, Republic of, 05505
        • Recruiting
        • Research Site
      • Seoul, Korea, Republic of, 06351
        • Recruiting
        • Research Site
      • Seoul, Korea, Republic of, 03080
        • Recruiting
        • Research Site
  • Spain
      • Barcelona, Spain, 08036
        • Recruiting
        • Research Site
      • Barcelona, Spain, 8035
        • Recruiting
        • Research Site
      • Madrid, Spain, 28007
        • Recruiting
        • Research Site
      • Madrid, Spain, 28040
        • Recruiting
        • Research Site
      • Pamplona, Spain, 31008
        • Recruiting
        • Research Site
  • Taiwan
      • Kaohsiung, Taiwan, 80756
        • Recruiting
        • Research Site
      • Kaohsiung city, Taiwan, 833
        • Recruiting
        • Research Site
      • Liuying, Taiwan, 736
        • Recruiting
        • Research Site
      • Taichung, Taiwan, 40705
        • Recruiting
        • Research Site
      • Tainan City, Taiwan, 70403
        • Recruiting
        • Research Site
      • Taipei, Taiwan, 10002
        • Recruiting
        • Research Site
      • Taipei, Taiwan, 11259
        • Recruiting
        • Research Site
      • Taoyuan, Taiwan, 333
        • Recruiting
        • Research Site
  • United Kingdom
      • Cambridge, United Kingdom, CB2 0QQ
        • Recruiting
        • Research Site
      • Edinburgh, United Kingdom, EH4 2XU
        • Withdrawn
        • Research Site
      • London, United Kingdom, NW3 2QG
        • Recruiting
        • Research Site
      • Manchester, United Kingdom, M20 4BX
        • Not yet recruiting
        • Research Site
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • Recruiting
        • Research Site
    • California
      • Costa Mesa, California, United States, 92627
        • Recruiting
        • Research Site
      • Orange, California, United States, 92868
        • Recruiting
        • Research Site
    • Florida
      • Miami Beach, Florida, United States, 33140
        • Withdrawn
        • Research Site
    • Indiana
      • Dyer, Indiana, United States, 46311
        • Withdrawn
        • Research Site
    • Kansas
      • Kansas City, Kansas, United States, 66103
        • Recruiting
        • Research Site
    • New York
      • New York, New York, United States, 10065
        • Recruiting
        • Research Site
    • Texas
      • Dallas, Texas, United States, 75251
        • Not yet recruiting
        • Research Site
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Not yet recruiting
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cohort 1A
Volrustomig monotherapy
Drug: Volrustomig
CTLA-4/Anti-PD-1 Bispecific Antibody
Experimental: Cohort 1B
Volrustomig combination with bevacizumab
Drug: Bevacizumab
15 mg/kg, IV (in the vein) on day 1 of each 21 day cycle. Number of Cycles: until disease progression or unacceptable toxicity develops.
Drug: Volrustomig
CTLA-4/Anti-PD-1 Bispecific Antibody
Experimental: Cohort 1C
Volrustomig combination with lenvatinib
Drug: Lenvatinib
Daily use per oral (8 mg capsules/day for participants < 60 kg or 12 mg/day for participants ≥ 60 kg) of 21 day cycle. Number of Cycles: until disease progression or unacceptable toxicity develops.
Drug: Volrustomig
CTLA-4/Anti-PD-1 Bispecific Antibody
Experimental: Cohort 2A
Rilvegostomig combination with Gemcitabine and Cisplatin
Drug: Gemcitabine
1000 mg/m2, IV infusion
Drug: Cisplatin
25 mg/m2, IV infusion
Drug: Rilvegostomig
anti- PD-1 and TIGIT bispecific antibody
Experimental: Cohort 2B
Volrustomig combination with Gemcitabine and Cisplatin
Drug: Gemcitabine
1000 mg/m2, IV infusion
Drug: Cisplatin
25 mg/m2, IV infusion
Drug: Volrustomig
CTLA-4/Anti-PD-1 Bispecific Antibody
Experimental: Cohort 1D
Volrustomig combination with rilvegostomig and bevacizumab
Drug: Bevacizumab
15 mg/kg, IV (in the vein) on day 1 of each 21 day cycle. Number of Cycles: until disease progression or unacceptable toxicity develops.
Drug: Volrustomig
CTLA-4/Anti-PD-1 Bispecific Antibody
Drug: Rilvegostomig
anti- PD-1 and TIGIT bispecific antibody
Experimental: Cohort 1E
Rilvegostomig combination with bevacizumab
Drug: Bevacizumab
15 mg/kg, IV (in the vein) on day 1 of each 21 day cycle. Number of Cycles: until disease progression or unacceptable toxicity develops.
Drug: Rilvegostomig
anti- PD-1 and TIGIT bispecific antibody

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The number of participants with adverse events/serious adverse events
Time Frame: 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.
Through study completion, an average of 2 years
Objective response rate (ORR)
Time Frame: 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)
Through study completion, an average of 2 years
Progression free survival (PFS)
Time Frame: 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)
Through study completion, an average of 2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective response rate (ORR)
Time Frame: 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
Through study completion, an average of 2 years
Duration Of Response (DOR)
Time Frame: 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.
Through study completion, an average of 2 years
Disease Control Rate (DCR)
Time Frame: 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.
At 12 and 24 weeks
Progression free survival (PFS)
Time Frame: 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.
Through study completion, an average of 2 years
Overall Survival (OS)
Time Frame: 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.
Through study completion, an average of 2 years
Anti Drug Antibody (ADA)
Time Frame: Through study completion, an average of 2 years
Incidences of ADAs against novel immunomodulators in serum.
Through study completion, an average of 2 years
Pharmacokinetics of novel immunomodulators: Maximum plasma concentration of the study drug (Cmax)
Time Frame: 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
From the first dose of study intervention, at predefined intervals throughout the administration of novel immunomodulators ( approx 2 years )
Pharmacokinetics of novel immunomodulators: Time to maximum plasma concentration of the study drug (T-max)
Time Frame: 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
From the first dose of study intervention, at predefined intervals throughout the administration of novel immunomodulators ( approx 2 years )
lmmunogenicity of novel immunomodulators
Time Frame: 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.
From the first dose of study intervention, at predefined intervals throughout the administration of novel immunomodulators ( approx 2 years)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AstraZeneca

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 24, 2023

Primary Completion (Estimated)

November 26, 2025

Study Completion (Estimated)

November 25, 2026

Study Registration Dates

First Submitted

March 2, 2023

First Submitted That Met QC Criteria

March 17, 2023

First Posted (Actual)

March 20, 2023

Study Record Updates

Last Update Posted (Actual)

April 12, 2024

Last Update Submitted That Met QC Criteria

April 11, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • D7987C00001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

IPD Sharing Time Frame

AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

IPD Sharing Access Criteria

When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Hepatocellular Carcinoma

Clinical Trials on Bevacizumab

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Malaysia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe