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

Primary Purpose

Hepatocellular Carcinoma, Biliary Tract Cancer

Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
MEDI5752
Bevacizumab
Lenvatinib
AZD2936
Gemcitabine
Cisplatin
Sponsored by
AstraZeneca
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatocellular Carcinoma focused on measuring Hepatobiliary cancer, Hepatocellular carcinoma, Biliary tract cancer, GEMINI-Hepatobiliary, MEDI5752, AZD2936, Bispecific antibody, Volrustomig, Rilvegostomig

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

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Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Cohort 1A

Cohort 1B

Cohort 1C

Cohort 2A

Cohort 2B

Arm Description

MEDI5752 monotherapy

MEDI5752 combination with bevacizumab

MEDI5752 combination with lenvatinib

AZD2936 combination with Gemcitabine and Cisplatin

MEDI5752 combination with Gemcitabine and Cisplatin

Outcomes

Primary Outcome Measures

Objective response rate (ORR)
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)
The number of participants with adverse events/serious adverse events
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)
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)

Secondary Outcome Measures

Duration Of Response (DOR)
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.
Disease Control Rate (DCR)
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.
Progression free survival (PFS)
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.
Overall Survival (OS)
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)
Incidences of ADAs against novel immunomodulators in serum.
Pharmacokinetics of novel immunomodulators: Maximum plasma concentration of the study drug (Cmax)
Maximum observed plasma concentration of the study drug
Pharmacokinetics of novel immunomodulators: Time to maximum plasma concentration of the study drug (T-max)
Time to maximum observed plasma concentration of the study drug
lmmunogenicity of novel immunomodulators
The number and percentage of participants who develop ADAs.
Objective response rate (ORR)
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

Full Information

First Posted
March 2, 2023
Last Updated
October 10, 2023
Sponsor
AstraZeneca
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1. Study Identification

Unique Protocol Identification Number
NCT05775159
Brief Title
Study of Novel Immunomodulators as Monotherapy and in Combination With Anticancer Agents in Participants With Advanced Hepatobiliary Cancer
Official Title
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)
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 24, 2023 (Actual)
Primary Completion Date
November 8, 2024 (Anticipated)
Study Completion Date
November 11, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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 MEDI5752 as monotherapy (MONO) and 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, MEDI5752 will be evaluated as monotherapy and in combination with bevacizumab or lenvatinib in approximately 120 evaluable participants with advanced HCC. In Substudy 2, the efficacy and safety of AZD2936 or MEDI5752 plus gemcitabine and cisplatin are investigated in approximately 60 evaluable participants with advanced BTC who have not received previous treatment for advanced/metastatic disease.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatocellular Carcinoma, Biliary Tract Cancer
Keywords
Hepatobiliary cancer, Hepatocellular carcinoma, Biliary tract cancer, GEMINI-Hepatobiliary, MEDI5752, AZD2936, Bispecific antibody, Volrustomig, Rilvegostomig

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
180 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1A
Arm Type
Experimental
Arm Description
MEDI5752 monotherapy
Arm Title
Cohort 1B
Arm Type
Experimental
Arm Description
MEDI5752 combination with bevacizumab
Arm Title
Cohort 1C
Arm Type
Experimental
Arm Description
MEDI5752 combination with lenvatinib
Arm Title
Cohort 2A
Arm Type
Experimental
Arm Description
AZD2936 combination with Gemcitabine and Cisplatin
Arm Title
Cohort 2B
Arm Type
Experimental
Arm Description
MEDI5752 combination with Gemcitabine and Cisplatin
Intervention Type
Drug
Intervention Name(s)
MEDI5752
Intervention Description
CTLA-4/Anti-PD-1 Bispecific Antibody
Intervention Type
Drug
Intervention Name(s)
Bevacizumab
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Lenvatinib
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
AZD2936
Intervention Description
anti- PD-1 and TIGIT bispecific antibody
Intervention Type
Drug
Intervention Name(s)
Gemcitabine
Intervention Description
1000 mg/m2, IV infusion
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Intervention Description
25 mg/m2, IV infusion
Primary Outcome Measure Information:
Title
Objective response rate (ORR)
Description
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)
Time Frame
Through study completion, an average of 2 years
Title
The number of participants with adverse events/serious adverse events
Description
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.
Time Frame
Through study completion, an average of 2 years
Title
Progression free survival (PFS)
Description
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)
Time Frame
Through study completion, an average of 2 years
Secondary Outcome Measure Information:
Title
Duration Of Response (DOR)
Description
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.
Time Frame
Through study completion, an average of 2 years
Title
Disease Control Rate (DCR)
Description
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.
Time Frame
At 12 and 24 weeks
Title
Progression free survival (PFS)
Description
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.
Time Frame
Through study completion, an average of 2 years
Title
Overall Survival (OS)
Description
OS is defined as the time from the start of study intervention until the date of death due to any cause, whichever occurs first.
Time Frame
Through study completion, an average of 2 years
Title
Anti Drug Antibody (ADA)
Description
Incidences of ADAs against novel immunomodulators in serum.
Time Frame
Through study completion, an average of 2 years
Title
Pharmacokinetics of novel immunomodulators: Maximum plasma concentration of the study drug (Cmax)
Description
Maximum observed plasma concentration of the study drug
Time Frame
From the first dose of study intervention, at predefined intervals throughout the administration of novel immunomodulators ( approx 2 years )
Title
Pharmacokinetics of novel immunomodulators: Time to maximum plasma concentration of the study drug (T-max)
Description
Time to maximum observed plasma concentration of the study drug
Time Frame
From the first dose of study intervention, at predefined intervals throughout the administration of novel immunomodulators ( approx 2 years )
Title
lmmunogenicity of novel immunomodulators
Description
The number and percentage of participants who develop ADAs.
Time Frame
From the first dose of study intervention, at predefined intervals throughout the administration of novel immunomodulators ( approx 2 years)
Title
Objective response rate (ORR)
Description
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
Time Frame
Through study completion, an average of 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
AstraZeneca Clinical Study Information Center
Phone
1-877-240-9479
Email
information.center@astrazeneca.com
Facility Information:
Facility Name
Research Site
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Research Site
City
Costa Mesa
State/Province
California
ZIP/Postal Code
92627
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Research Site
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Research Site
City
Miami Beach
State/Province
Florida
ZIP/Postal Code
33140
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Research Site
City
Dyer
State/Province
Indiana
ZIP/Postal Code
46311
Country
United States
Individual Site Status
Suspended
Facility Name
Research Site
City
Fairway
State/Province
Kansas
ZIP/Postal Code
66205
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Research Site
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Research Site
City
Dallas
State/Province
Texas
ZIP/Postal Code
75251
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Research Site
City
Fairfax
State/Province
Virginia
ZIP/Postal Code
22031
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Research Site
City
Beijing
ZIP/Postal Code
100050
Country
China
Individual Site Status
Not yet recruiting
Facility Name
Research Site
City
Beijing
ZIP/Postal Code
100142
Country
China
Individual Site Status
Not yet recruiting
Facility Name
Research Site
City
Chengdu
ZIP/Postal Code
610000
Country
China
Individual Site Status
Not yet recruiting
Facility Name
Research Site
City
Chengdu
ZIP/Postal Code
610041
Country
China
Individual Site Status
Recruiting
Facility Name
Research Site
City
Chongqing
ZIP/Postal Code
400030
Country
China
Individual Site Status
Not yet recruiting
Facility Name
Research Site
City
Fuzhou
ZIP/Postal Code
350007
Country
China
Individual Site Status
Recruiting
Facility Name
Research Site
City
Guangzhou
ZIP/Postal Code
510060
Country
China
Individual Site Status
Not yet recruiting
Facility Name
Research Site
City
Guangzhou
ZIP/Postal Code
510515
Country
China
Individual Site Status
Recruiting
Facility Name
Research Site
City
Harbin
ZIP/Postal Code
150081
Country
China
Individual Site Status
Recruiting
Facility Name
Research Site
City
Hefei
ZIP/Postal Code
230001
Country
China
Individual Site Status
Not yet recruiting
Facility Name
Research Site
City
Hefei
ZIP/Postal Code
230022
Country
China
Individual Site Status
Not yet recruiting
Facility Name
Research Site
City
Hefei
ZIP/Postal Code
230601
Country
China
Individual Site Status
Not yet recruiting
Facility Name
Research Site
City
Nanchang
ZIP/Postal Code
330006
Country
China
Individual Site Status
Recruiting
Facility Name
Research Site
City
Nanning
ZIP/Postal Code
530021
Country
China
Individual Site Status
Not yet recruiting
Facility Name
Research Site
City
Shandong
Country
China
Individual Site Status
Not yet recruiting
Facility Name
Research Site
City
Shanghai
ZIP/Postal Code
200032
Country
China
Individual Site Status
Recruiting
Facility Name
Research Site
City
Shanghai
ZIP/Postal Code
200032
Country
China
Individual Site Status
Not yet recruiting
Facility Name
Research Site
City
Xi'an
ZIP/Postal Code
710038
Country
China
Individual Site Status
Not yet recruiting
Facility Name
Research Site
City
Zhengzhou
ZIP/Postal Code
450008
Country
China
Individual Site Status
Withdrawn
Facility Name
Research Site
City
Hong Kong
ZIP/Postal Code
150001
Country
Hong Kong
Individual Site Status
Not yet recruiting
Facility Name
Research Site
City
Shatin
ZIP/Postal Code
00000
Country
Hong Kong
Individual Site Status
Recruiting
Facility Name
Research Site
City
Firenze
ZIP/Postal Code
50134
Country
Italy
Individual Site Status
Recruiting
Facility Name
Research Site
City
Milano
ZIP/Postal Code
20132
Country
Italy
Individual Site Status
Recruiting
Facility Name
Research Site
City
Napoli
ZIP/Postal Code
80131
Country
Italy
Individual Site Status
Recruiting
Facility Name
Research Site
City
Rozzano
ZIP/Postal Code
20089
Country
Italy
Individual Site Status
Recruiting
Facility Name
Research Site
City
Chuo-ku
ZIP/Postal Code
104-0045
Country
Japan
Individual Site Status
Not yet recruiting
Facility Name
Research Site
City
Kashiwa
ZIP/Postal Code
277-8577
Country
Japan
Individual Site Status
Recruiting
Facility Name
Research Site
City
Yokohama-shi
ZIP/Postal Code
241-8515
Country
Japan
Individual Site Status
Recruiting
Facility Name
Research Site
City
Seongnam-Si
ZIP/Postal Code
463-712
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Research Site
City
Seoul
ZIP/Postal Code
03722
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Research Site
City
Seoul
ZIP/Postal Code
05505
Country
Korea, Republic of
Individual Site Status
Not yet recruiting
Facility Name
Research Site
City
Seoul
ZIP/Postal Code
06351
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Research Site
City
Seoul
ZIP/Postal Code
13620
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Research Site
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Individual Site Status
Recruiting
Facility Name
Research Site
City
Barcelona
ZIP/Postal Code
8035
Country
Spain
Individual Site Status
Recruiting
Facility Name
Research Site
City
Madrid
ZIP/Postal Code
28007
Country
Spain
Individual Site Status
Not yet recruiting
Facility Name
Research Site
City
Madrid
ZIP/Postal Code
28040
Country
Spain
Individual Site Status
Recruiting
Facility Name
Research Site
City
Pamplona
ZIP/Postal Code
31008
Country
Spain
Individual Site Status
Not yet recruiting
Facility Name
Research Site
City
Kaohsiung city
ZIP/Postal Code
833
Country
Taiwan
Individual Site Status
Recruiting
Facility Name
Research Site
City
Kaohsiung
ZIP/Postal Code
80756
Country
Taiwan
Individual Site Status
Recruiting
Facility Name
Research Site
City
Liuying
ZIP/Postal Code
736
Country
Taiwan
Individual Site Status
Recruiting
Facility Name
Research Site
City
Taichung
ZIP/Postal Code
40705
Country
Taiwan
Individual Site Status
Recruiting
Facility Name
Research Site
City
Tainan City
ZIP/Postal Code
70403
Country
Taiwan
Individual Site Status
Recruiting
Facility Name
Research Site
City
Taipei
ZIP/Postal Code
10002
Country
Taiwan
Individual Site Status
Recruiting
Facility Name
Research Site
City
Taoyuan
ZIP/Postal Code
333
Country
Taiwan
Individual Site Status
Recruiting
Facility Name
Research Site
City
Cambridge
ZIP/Postal Code
CB2 0QQ
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Research Site
City
Edinburgh
ZIP/Postal Code
EH4 2XU
Country
United Kingdom
Individual Site Status
Not yet recruiting
Facility Name
Research Site
City
London
ZIP/Postal Code
NW3 2QG
Country
United Kingdom
Individual Site Status
Not yet recruiting
Facility Name
Research Site
City
Manchester
ZIP/Postal Code
M20 4BX
Country
United Kingdom
Individual Site Status
Not yet recruiting

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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 URL
https://astrazenecagroup-dt.pharmacm.com/DT/Home

Learn more about this trial

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

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