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

Hepatocellular Carcinoma Clinical Trial

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05775159
• Other study ID #: D7987C00001
• Status: Recruiting
• Phase: Phase 2
• Start date: April 24, 2023
• Est. completion date: November 25, 2026

Study information

• Verified date: April 2024
• Source: AstraZeneca
• Contact: AstraZeneca Clinical Study Information Center
• Phone: 1-877-240-9479
• Email: information.center[@]astrazeneca.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 260
• Est. completion date: November 25, 2026
• Est. primary completion date: November 26, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Biliary Tract Cancer
• Biliary Tract Neoplasms
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

Intervention

Drug:
• Volrustomig
CTLA-4/Anti-PD-1 Bispecific Antibody
• 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.
• 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.
• Rilvegostomig
anti- PD-1 and TIGIT bispecific antibody
• Gemcitabine
1000 mg/m2, IV infusion
• Cisplatin
25 mg/m2, IV infusion

Locations

Country	Name	City	State
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Chengdu
China	Research Site	Chengdu
China	Research Site	Chongqing
China	Research Site	Fuzhou
China	Research Site	Guangzhou
China	Research Site	Guangzhou
China	Research Site	Harbin
China	Research Site	Hefei
China	Research Site	Hefei
China	Research Site	Hefei
China	Research Site	Nanchang
China	Research Site	Nanning
China	Research Site	Shandong
China	Research Site	Shanghai
China	Research Site	Xi'an
China	Research Site	Zhengzhou
Hong Kong	Research Site	Hong Kong
Hong Kong	Research Site	Shatin
Italy	Research Site	Firenze
Italy	Research Site	Milano
Italy	Research Site	Napoli
Italy	Research Site	Rozzano
Japan	Research Site	Chuo-ku
Japan	Research Site	Kashiwa
Japan	Research Site	Yokohama-shi
Korea, Republic of	Research Site	Seongnam-Si
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Pamplona
Taiwan	Research Site	Kaohsiung
Taiwan	Research Site	Kaohsiung city
Taiwan	Research Site	Liuying
Taiwan	Research Site	Taichung
Taiwan	Research Site	Tainan City
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taoyuan
United Kingdom	Research Site	Cambridge
United Kingdom	Research Site	Edinburgh
United Kingdom	Research Site	London
United Kingdom	Research Site	Manchester
United States	Research Site	Birmingham	Alabama
United States	Research Site	Costa Mesa	California
United States	Research Site	Dallas	Texas
United States	Research Site	Dyer	Indiana
United States	Research Site	Fairfax	Virginia
United States	Research Site	Kansas City	Kansas
United States	Research Site	Miami Beach	Florida
United States	Research Site	New York	New York
United States	Research Site	Orange	California

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  China,  Hong Kong,  Italy,  Japan,  Korea, Republic of,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	Through study completion, an average of 2 years
Primary	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.	Through study completion, an average of 2 years
Primary	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)	Through study completion, an average of 2 years
Secondary	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.	Through study completion, an average of 2 years
Secondary	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.	At 12 and 24 weeks
Secondary	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.	Through study completion, an average of 2 years
Secondary	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.	Through study completion, an average of 2 years
Secondary	Anti Drug Antibody (ADA)	Incidences of ADAs against novel immunomodulators in serum.	Through study completion, an average of 2 years
Secondary	Pharmacokinetics of novel immunomodulators: Maximum plasma concentration of the study drug (Cmax)	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 )
Secondary	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	From the first dose of study intervention, at predefined intervals throughout the administration of novel immunomodulators ( approx 2 years )
Secondary	lmmunogenicity of novel immunomodulators	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)
Secondary	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	Through study completion, an average of 2 years