Clinical trial NCT05775159: 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
Overall status: RECRUITING
Phase: PHASE2
Conditions: Hepatocellular Carcinoma
Biliary Tract Cancer
Keywords: Hepatobiliary cancer
Hepatocellular carcinoma
Biliary tract cancer
GEMINI-Hepatobiliary
MEDI5752
AZD2936
Bispecific antibody
Volrustomig
Rilvegostomig
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2023-03-20
Enrollment: 260
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Objective response rate (ORR)
timeFrame: Through study completion, an average of 2 years
measure: The number of participants with adverse events/serious adverse events
timeFrame: Through study completion, an average of 2 years
measure: Progression free survival (PFS)
timeFrame: Through study completion, an average of 2 years
Secondary outcomes:
measure: Duration Of Response (DOR)
timeFrame: Through study completion, an average of 2 years
measure: Disease Control Rate (DCR)
timeFrame: At 12 and 24 weeks
measure: Progression free survival (PFS)
timeFrame: Through study completion, an average of 2 years
measure: Overall Survival (OS)
timeFrame: Through study completion, an average of 2 years
measure: Anti Drug Antibody (ADA)
timeFrame: Through study completion, an average of 2 years
measure: Pharmacokinetics of novel immunomodulators: Maximum plasma concentration of the study drug (Cmax)
timeFrame: From the first dose of study intervention, at predefined intervals throughout the administration of novel immunomodulators ( approx 2 years )
measure: Pharmacokinetics of novel immunomodulators: Time to maximum plasma concentration of the study drug (T-max)
timeFrame: From the first dose of study intervention, at predefined intervals throughout the administration of novel immunomodulators ( approx 2 years )
measure: lmmunogenicity of novel immunomodulators
timeFrame: From the first dose of study intervention, at predefined intervals throughout the administration of novel immunomodulators ( approx 2 years)
measure: Objective response rate (ORR)
timeFrame: Through study completion, an average of 2 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Research Site
state: Alabama
city: Costa Mesa
country: United States
facility: Research Site
state: California
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Orange
country: United States
facility: Research Site
state: California
city: Miami Beach
country: United States
facility: Research Site
state: Florida
city: Dyer
country: United States
facility: Research Site
state: Indiana
city: Kansas City
country: United States
facility: Research Site
state: Kansas
city: New York
country: United States
facility: Research Site
state: New York
city: Dallas
country: United States
facility: Research Site
state: Texas
city: Fairfax
country: United States
facility: Research Site
state: Virginia
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Chengdu
country: China
facility: Research Site
city: Chengdu
country: China
facility: Research Site
city: Chongqing
country: China
facility: Research Site
city: Fuzhou
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Harbin
country: China
facility: Research Site
city: Hefei
country: China
facility: Research Site
city: Hefei
country: China
facility: Research Site
city: Hefei
country: China
facility: Research Site
city: Nanchang
country: China
facility: Research Site
city: Nanning
country: China
facility: Research Site
city: Shandong
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Xi'an
country: China
facility: Research Site
city: Zhengzhou
country: China
facility: Research Site
city: Hong Kong
country: Hong Kong
facility: Research Site
city: Hong Kong
country: Hong Kong
facility: Research Site
city: Shatin
country: Hong Kong
facility: Research Site
city: Firenze
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Napoli
country: Italy
facility: Research Site
city: Rozzano
country: Italy
facility: Research Site
city: Chuo-ku
country: Japan
facility: Research Site
city: Kashiwa
country: Japan
facility: Research Site
city: Yokohama-shi
country: Japan
facility: Research Site
city: Seongnam-Si
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Pamplona
country: Spain
facility: Research Site
city: Kaohsiung city
country: Taiwan
facility: Research Site
city: Kaohsiung
country: Taiwan
facility: Research Site
city: Liuying
country: Taiwan
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Tainan City
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taoyuan
country: Taiwan
facility: Research Site
city: Cambridge
country: United Kingdom
facility: Research Site
city: Edinburgh
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
Study officials:
References: