Novel Combinations in Participants With Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma

Sponsor

AstraZeneca (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05702229

Collaborator

(none)

Enrollment

Locations

Arms

26.1

Anticipated Duration (Months)

3.1

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a Phase II, open-label, multi-drug, multi-centre study designed to assess the efficacy, safety, tolerability, pharmacokinetics, and immunogenicity of novel combination therapies in participants with locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma.

Condition or Disease	Intervention/Treatment	Phase
Gastric Cancer	Drug: AZD2936 Drug: MEDI5752 Drug: FOLFOX Drug: XELOX	Phase 2

Detailed Description

Approximately 80 participants will be assigned across two substudies, with approximately 40 evaluable participants for study intervention in each corresponding substudy.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

80 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

An Open-Label, Multi-Drug, Multi-Centre, Phase II Study to Evaluate the Efficacy, Safety, Tolerability, Pharmacokinetics, and Immunogenicity of Novel Combinations in Participants With Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma

Actual Study Start Date :

Jan 16, 2023

Anticipated Primary Completion Date :

Jun 25, 2024

Anticipated Study Completion Date :

Mar 21, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Substudy 1 MEDI5752 Plus XELOX/FOLFOX	Drug: MEDI5752 a PD-1 and CTLA-4 bispecific antibody; IV infusion Drug: FOLFOX 5-fluorouracil 400 mg/m^2 IV, oxaliplatin 85 mg/m^2, leucovorin 400 mg/m^2 (or levoleucovorin 200 mg/m^2 when locally preferred and available), day 1, 5-fluorouracil 1200 mg/m^2 IV 24 h day 1-2 Drug: XELOX capecitabine 1000 mg/m^2 BID, days 1 to 14, oxaliplatin 130 mg/m^2, day 1
Experimental: Substudy 2 AZD2936 Plus XELOX/FOLFOX	Drug: AZD2936 a PD-1 and TIGIT bispecific antibody; IV infusion Drug: FOLFOX 5-fluorouracil 400 mg/m^2 IV, oxaliplatin 85 mg/m^2, leucovorin 400 mg/m^2 (or levoleucovorin 200 mg/m^2 when locally preferred and available), day 1, 5-fluorouracil 1200 mg/m^2 IV 24 h day 1-2 Drug: XELOX capecitabine 1000 mg/m^2 BID, days 1 to 14, oxaliplatin 130 mg/m^2, day 1

Arm

Intervention/Treatment

Experimental: Substudy 1

MEDI5752 Plus XELOX/FOLFOX

Drug: MEDI5752

a PD-1 and CTLA-4 bispecific antibody; IV infusion

Drug: FOLFOX

5-fluorouracil 400 mg/m^2 IV, oxaliplatin 85 mg/m^2, leucovorin 400 mg/m^2 (or levoleucovorin 200 mg/m^2 when locally preferred and available), day 1, 5-fluorouracil 1200 mg/m^2 IV 24 h day 1-2

Drug: XELOX

capecitabine 1000 mg/m^2 BID, days 1 to 14, oxaliplatin 130 mg/m^2, day 1

Experimental: Substudy 2

AZD2936 Plus XELOX/FOLFOX

Drug: AZD2936

a PD-1 and TIGIT bispecific antibody; IV infusion

Drug: FOLFOX

5-fluorouracil 400 mg/m^2 IV, oxaliplatin 85 mg/m^2, leucovorin 400 mg/m^2 (or levoleucovorin 200 mg/m^2 when locally preferred and available), day 1, 5-fluorouracil 1200 mg/m^2 IV 24 h day 1-2

Drug: XELOX

capecitabine 1000 mg/m^2 BID, days 1 to 14, oxaliplatin 130 mg/m^2, day 1

Outcome Measures

Primary Outcome Measures

ORR (per RECIST 1.1 as assessed by Investigator) [Through study completion, an average of 2 years]
the proportion of participants who have a confirmed complete response or confirmed partial response, as determined by the Investigator at local site per RECIST 1.1.
PFS6 (per RECIST 1.1 as assessed by Investigator) [Through study completion, an average of 2 years]
the proportion of participants alive and progression-free at 6 months.

Secondary Outcome Measures

PFS per RECIST 1.1 as assessed by the Investigator [Through study completion, an average of 2 years]
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.
OS [Through study completion, an average of 2 years]
the time from the start of study intervention until the date of death due to any cause.
other safety related endpoints [Through study completion, an average of 2 years]
Incidence of AEs, AESIs, and SAEs

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

18 years or older at the time of signing the ICF.
Body weight > 35 kg.
Previously untreated for unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma.
Has measurable target disease assessed by the Investigator based on RECIST 1.1.
ECOG PS 0 or 1.
Life expectancy of at least 12 weeks.
Adequate organ and bone marrow function.

Exclusion Criteria:

Participants with HER2-positive (3+ by IHC, or 2+ by IHC and positive by ISH] or indeterminate gastric or GEJ carcinoma.
Untreated or progressive CNS metastatic disease, any leptomeningeal disease, or cord compression.
Participants with ascites which cannot be controlled with appropriate interventions.
Active infectious diseases, including tuberculosis, HIV infection, or hepatitis A/B/C.
Uncontrolled intercurrent illness.
Active or prior documented autoimmune or inflammatory disorders requiring systemic treatment with steroids or other immunosuppressive treatment.
History of another primary malignancy.
Previous treatment with an immune-oncology agent.

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Research Site	Beijing	China	100142
2	Research Site	Hangzhou	China	310003
3	Research Site	Hangzhou	China	310020
4	Research Site	Harbin	China	150081
5	Research Site	Hefei	China	230031
6	Research Site	Wuhan	China	430079
7	Research Site	Yinchuan	China	750004
8	Research Site	Zhengzhou	China
9	Research Site	Seoul	Korea, Republic of	03722
10	Research Site	Seoul	Korea, Republic of	05505
11	Research Site	Seoul	Korea, Republic of	13620
12	Research Site	Seoul	Korea, Republic of	6351
13	Research Site	Barcelona	Spain	08035
14	Research Site	Elche(Alicante)	Spain	03202
15	Research Site	L'Hospitalet de Llobregat	Spain	08908
16	Research Site	Madrid	Spain	28007
17	Research Site	Madrid	Spain	28040
18	Research Site	Santander	Spain	39008
19	Research Site	Hsinchu	Taiwan	300
20	Research Site	Kaohsiung	Taiwan	80756
21	Research Site	Taichung	Taiwan	404
22	Research Site	Tainan City	Taiwan	70403
23	Research Site	Taipei	Taiwan	10002
24	Research Site	Taipei	Taiwan	11259
25	Research Site	Taoyuan City	Taiwan	333
26	Research Site	Oxford	United Kingdom	OX3 7LE