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

• Sponsor: AstraZeneca (Industry)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT05775159
• Collaborator: (none)
• Enrollment: 120
• Locations: 45
• Arms: 3
• Anticipated Duration (Months): 30.7
• Patients Per Site: 2.7
• Patients Per Site Per Month: 0.1

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Hepatocellular Carcinoma; Biliary Tract Cancer	Drug: MEDI5752; Drug: Bevacizumab; Drug: Lenvatinib	Phase 2

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.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 120 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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)
• Anticipated Study Start Date: Apr 6, 2023
• Anticipated Primary Completion Date: Oct 28, 2024
• Anticipated Study Completion Date: Oct 27, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1A MEDI5752 monotherapy	Drug: MEDI5752; CTLA-4/Anti-PD-1 Bispecific Antibody
Experimental: Cohort 1B MEDI5752 combination with bevacizumab	Drug: MEDI5752; CTLA-4/Anti-PD-1 Bispecific Antibody; Drug: 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.
Experimental: Cohort 1C MEDI5752 combination with lenvatinib	Drug: MEDI5752; CTLA-4/Anti-PD-1 Bispecific Antibody; Drug: 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.

Outcome Measures

Primary Outcome Measures

1. 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

2. 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.

Secondary Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

5. Anti Drug Antibody (ADA) [Through study completion, an average of 2 years]

   Incidences of ADAs against novel immunomodulators in serum.

6. 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

7. 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

8. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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 or in the waiting-list 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.

• History of hepatic encephalopathy within 12 months prior to treatment allocation.

• Previous treatment in the present study.

• For substudy 1, participants co-infected with HBV and hepatitis D virus (HDV).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Birmingham	Alabama	United States	35233
2	Research Site	Orange	California	United States	92868
3	Research Site	Miami Beach	Florida	United States	33140
4	Research Site	Beijing		China	100050
5	Research Site	Beijing		China	100142
6	Research Site	Chengdu		China	610000
7	Research Site	Chengdu		China	610041
8	Research Site	Chongqing		China	400030
9	Research Site	Fuzhou		China	350005
10	Research Site	Guangzhou		China	510060
11	Research Site	Guangzhou		China	510515
12	Research Site	Harbin		China	150081
13	Research Site	Hefei		China	230001
14	Research Site	Hefei		China	230022
15	Research Site	Hefei		China	230601
16	Research Site	Nanchang		China	330006
17	Research Site	Nanning		China	530021
18	Research Site	Shandong		China
19	Research Site	Shanghai		China	200032
20	Research Site	Xi'an		China	710038
21	Research Site	Zhengzhou		China	450008
22	Research Site	Hong Kong		Hong Kong	150001
23	Research Site	Firenze		Italy	50134
24	Research Site	Milano		Italy	20132
25	Research Site	Napoli		Italy	80131
26	Research Site	Rozzano		Italy	20089
27	Research Site	Seongnam-si		Korea, Republic of	463-712
28	Research Site	Seoul		Korea, Republic of	03722
29	Research Site	Seoul		Korea, Republic of	05505
30	Research Site	Seoul		Korea, Republic of	06351
31	Research Site	Seoul		Korea, Republic of	13620
32	Research Site	Barcelona		Spain	08036
33	Research Site	Barcelona		Spain	8035
34	Research Site	Madrid		Spain	28007
35	Research Site	Madrid		Spain	28040
36	Research Site	Pamplona		Spain	31008
37	Research Site	Kaohsiung city		Taiwan	833
38	Research Site	Kaohsiung		Taiwan	80756
39	Research Site	Liuying		Taiwan	736
40	Research Site	Taichung		Taiwan	40705
41	Research Site	Tainan City		Taiwan	70403
42	Research Site	Taipei		Taiwan	10002
43	Research Site	Taoyuan		Taiwan	333
44	Research Site	London		United Kingdom	NW3 2QG
45	Research Site	Manchester		United Kingdom	M20 4BX

Sponsors and Collaborators

• AstraZeneca

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT05775159
• Other Study ID Numbers: D7987C00001
• First Posted: Mar 20, 2023
• Last Update Posted: Mar 20, 2023
• Last Verified: Mar 1, 2023

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by AstraZeneca: Hepatobiliary cancer; Hepatocellular carcinoma; Biliary tract cancer; GEMINI-Hepatobiliary; MEDI5752; Bispecific antibody
• Additional relevant MeSH terms: Carcinoma, Hepatocellular; Biliary Tract Neoplasms; Bevacizumab; Lenvatinib

Study Results

No Results Posted as of Mar 20, 2023