Biliary Tract Cancer, Hepatocellular Carcinoma
Conditions
Keywords
Hepatobiliary cancer, Hepatocellular carcinoma, Biliary tract cancer, GEMINI-Hepatobiliary, MEDI5752, AZD2936, Bispecific antibody, Volrustomig, Rilvegostomig
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 90 evaluable participants with advanced BTC who have not received previous treatment for advanced/metastatic disease.
Interventions
DRUGVolrustomig
CTLA-4/Anti-PD-1 Bispecific Antibody
DRUGBevacizumab
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.
DRUGLenvatinib
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.
DRUGRilvegostomig
anti- PD-1 and TIGIT bispecific antibody
DRUGGemcitabine
1000 mg/m2, IV infusion
DRUGCisplatin
25 mg/m2, IV infusion
Sponsors
AstraZeneca
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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. |
| 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 |
| 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. |
| 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. |
| 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. |
Countries
China, Hong Kong, Italy, Japan, South Korea, Spain, Taiwan, United Kingdom, United States
Outcome results
None listed