Hepatocellular CarcinomaPhase 2NCT05775159
Study of Novel Immunomodulators as Monotherapy and in Combination With Anticancer Agents in Participants With Advanced Hepatobiliary Cancer
A Phase 2 study testing Volrustomig, Bevacizumab and Lenvatinib in people with Hepatocellular Carcinoma and Biliary Tract Cancer, run by AstraZeneca at 46 sites in 9 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatocellular Carcinoma, Biliary Tract Cancer
- What is being tested?
- Volrustomig, Bevacizumab and Lenvatinib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 294 participants
- Where
- 46 sitesin 9 countries
- Study dates
- 24 Apr 2023to 28 Oct 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
46 sites in 9 countries.
46 sites in 9 countries
China12 sites
Research Site
Beijing, 100050
Research Site
Beijing, 100142
Research Site
Beijing, 101100
Research Site
Chengdu, 610000
Research Site
Chengdu, 610041
Research Site
Chongqing, 400030
Research Site
Fuzhou, 350007
Research Site
Guangzhou, 510060
Research Site
Guangzhou, 510515
Research Site
Harbin, 150081
Research Site
Nanning, 530021
Research Site
Shanghai, 200032
Taiwan7 sites
Research Site
Kaohsiung City, 80756
Research Site
Kaohsiung City, 833
Research Site
Taichung, 407219
Research Site
Tainan, 70403
Research Site
Tainan, 710
Research Site
Taipei, 10002
Research Site
Taoyuan, 333
United States5 sites
Research Site
Birmingham, Alabama, 35233
Research Site
Kansas City, Kansas, 66103
Research Site
Los Angeles, California, 90089
Research Site
New York, New York, 10065
Research Site
Orange, California, 92868
South Korea5 sites
Research Site
Seongnam-si, 463-712
Research Site
Seoul, 03080
Research Site
Seoul, 03722
Research Site
Seoul, 05505
Research Site
Seoul, 06351
Spain5 sites
Research Site
Barcelona, 08036
Research Site
Barcelona, 8035
Research Site
Madrid, 28007
Research Site
Madrid, 28040
Research Site
Pamplona, 31008
Italy4 sites
Research Site
Florence, 50134
Research Site
Milan, 20132
Research Site
Naples, 80131
Research Site
Rozzano, 20089
Japan3 sites
Research Site
Chūōku, 104-0045
Research Site
Kashiwa, 277-8577
Research Site
Yokohama, 241-8515
United Kingdom3 sites
Research Site
Cambridge, CB2 0QQ
Research Site
London, NW3 2QG
Research Site
Manchester, M20 4BX
About this study
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)
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.
Read the 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.
- Conditions
- Hepatocellular Carcinoma, Biliary Tract Cancer
- Being tested
- Volrustomig, Bevacizumab, Lenvatinib, Rilvegostomig, Gemcitabine
- Keywords
- Hepatobiliary cancer, Hepatocellular carcinoma, Biliary tract cancer, GEMINI-Hepatobiliary, MEDI5752, AZD2936, Bispecific antibody, Volrustomig, Rilvegostomig
- Medical subject headings
- Carcinoma, Hepatocellular, Biliary Tract Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VolrustomigDrug
CTLA-4/Anti-PD-1 Bispecific Antibody
BevacizumabDrug
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.
LenvatinibDrug
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.
RilvegostomigDrug
anti- PD-1 and TIGIT bispecific antibody
GemcitabineDrug
1000 mg/m2, IV infusion
CisplatinDrug
25 mg/m2, IV infusion
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1A | Experimental | Volrustomig monotherapy Receives: Drug: Volrustomig |
| Cohort 1B | Experimental | Volrustomig combination with bevacizumab Receives: Drug: Volrustomig; Drug: Bevacizumab |
| Cohort 1C | Experimental | Volrustomig combination with lenvatinib Receives: Drug: Volrustomig; Drug: Lenvatinib |
| Cohort 2A | Experimental | Rilvegostomig combination with Gemcitabine and Cisplatin Receives: Drug: Rilvegostomig; Drug: Gemcitabine; Drug: Cisplatin |
| Cohort 2B | Experimental | Volrustomig combination with Gemcitabine and Cisplatin Receives: Drug: Volrustomig; Drug: Gemcitabine; Drug: Cisplatin |
| Cohort 1D | Experimental | Volrustomig combination with rilvegostomig and bevacizumab Receives: Drug: Volrustomig; Drug: Bevacizumab; Drug: Rilvegostomig |
| Cohort 1E | Experimental | Rilvegostomig combination with bevacizumab Receives: Drug: Bevacizumab; Drug: Rilvegostomig |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: Through study completion, an average of 2 years
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.
Measured: Through study completion, an average of 2 years
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)
Measured: Through study completion, an average of 2 years
Secondary outcomes (9)
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.
Measured: Through study completion, an average of 2 years
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.
Measured: At 12 and 24 weeks
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.
Measured: Through study completion, an average of 2 years
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.
Measured: Through study completion, an average of 2 years
Anti Drug Antibody (ADA)
Incidences of ADAs against novel immunomodulators in serum.
Measured: Through study completion, an average of 2 years
Pharmacokinetics of novel immunomodulators: Maximum plasma concentration of the study drug (Cmax)
Maximum observed plasma concentration of the study drug
Measured: 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 to maximum observed plasma concentration of the study drug
Measured: From the first dose of study intervention, at predefined intervals throughout the administration of novel immunomodulators ( approx 2 years )
lmmunogenicity of novel immunomodulators
The number and percentage of participants who develop ADAs.
Measured: From the first dose of study intervention, at predefined intervals throughout the administration of novel immunomodulators ( approx 2 years)
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
Measured: Through study completion, an average of 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Mar 2023
- Study start24 Apr 2023
- Primary completion27 Oct 2026 (estimated)
- Study completion28 Oct 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 294 participants (estimated)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05775159
- Sponsor's protocol ID
- D7987C00001
- Status last verified
- Aug 2026
- First submitted
- 2 Mar 2023
- Last updated
- 24 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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
Study at a glance
From the registry record, last updated by the sponsor on 24 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT05775159
- Acronym / sponsor ID
- D7987C00001
- Conditions
- Hepatocellular Carcinoma, Biliary Tract Cancer
- Keywords
- Hepatobiliary cancer, Hepatocellular carcinoma, Biliary tract cancer, GEMINI-Hepatobiliary, MEDI5752, AZD2936, Bispecific antibody, Volrustomig
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 294 participants (estimated)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 24 Apr 2023 (actual)
- Primary completion
- 27 Oct 2026 (estimated)
- Study completion
- 28 Oct 2027 (estimated)
- First posted
- 20 Mar 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| Cohort 1A | Experimental | Drug: VolrustomigVolrustomig monotherapy |
| Cohort 1B | Experimental | Drug: Volrustomig, Drug: BevacizumabVolrustomig combination with bevacizumab |
| Cohort 1C | Experimental | Drug: Volrustomig, Drug: LenvatinibVolrustomig combination with lenvatinib |
| Cohort 2A | Experimental | Drug: Rilvegostomig, Drug: Gemcitabine, Drug: CisplatinRilvegostomig combination with Gemcitabine and Cisplatin |
| Cohort 2B | Experimental | Drug: Volrustomig, Drug: Gemcitabine, Drug: CisplatinVolrustomig combination with Gemcitabine and Cisplatin |
| Cohort 1D | Experimental | Drug: Volrustomig, Drug: Bevacizumab, Drug: RilvegostomigVolrustomig combination with rilvegostomig and bevacizumab |
| Cohort 1E | Experimental | Drug: Bevacizumab, Drug: RilvegostomigRilvegostomig combination with bevacizumab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VolrustomigCTLA-4/Anti-PD-1 Bispecific Antibody | Drug | Cohort 1A, Cohort 1B, Cohort 1C, Cohort 1D, Cohort 2B |
| Bevacizumab15 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 | Cohort 1B, Cohort 1D, Cohort 1E |
| LenvatinibDaily 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 | Cohort 1C |
| Rilvegostomiganti- PD-1 and TIGIT bispecific antibody | Drug | Cohort 1D, Cohort 1E, Cohort 2A |
| Gemcitabine1000 mg/m2, IV infusion | Drug | Cohort 2A, Cohort 2B |
| Cisplatin25 mg/m2, IV infusion | Drug | Cohort 2A, Cohort 2B |
Primary outcome
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)
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.
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)
9 secondary outcomes
Duration Of Response (DOR)
Time frame: Through study completion, an average of 2 years
Disease Control Rate (DCR)
Time frame: At 12 and 24 weeks
Progression free survival (PFS)
Time frame: Through study completion, an average of 2 years
Overall Survival (OS)
Time frame: Through study completion, an average of 2 years
Anti Drug Antibody (ADA)
Time frame: 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 )
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 )
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)
Objective response rate (ORR)
Time frame: Through study completion, an average of 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Aug 2026.
- Individual participant dataSharing planned: Yes. 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
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
46 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Volrustomig, Bevacizumab and Lenvatinib in people with Hepatocellular Carcinoma and Biliary Tract Cancer, run by AstraZeneca at 46 sites in 9 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 24 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 46 sites in China, Taiwan, United States, South Korea, Spain and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective response rate (ORR) (time frame: Through study completion, an average of 2 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Aug 2026.