Clinical trial NCT05702229: Novel Combinations in Participants With Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Gastric Cancer
Keywords: Locally advanced
Metatstatic
Gastric adenocarcinoma
GEJ adenocarcinoma
GEMINI-Gastric
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2023-01-27
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: Approximately 240 participants will be assigned across 6 substudies, with approximately 40 evaluable participants of the confirmed recommend dose by SRC for study intervention in each corresponding substudy.

Eligibility criteria: 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 zero or one.
* Life expectancy of at least 12 weeks.
* Adequate organ and bone marrow function.
* Has central lab confirmed Claudin18.2 status at screening from archival tumour collected within past 24 months or from a fresh biopsy when Substudy 3, Substudy 4 or Substudy 6 is open for recruitment.

Exclusion Criteria:

* Participants with HER2-positive (3+ by IHC, or 2+ by IHC and positive by in situhybridisation) 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.
* Previous treatment with any modalities of Claudin18.2 target therapy or MMAE exposure (when Substudy 3, Substudy 4, or Substudy 6 is open for recruitment).

Primary outcomes:
measure: ORR (per RECIST 1.1 as assessed by Investigator)
timeFrame: Through substudy completion, an average of 2 years
measure: PFS6 (per RECIST 1.1 as assessed by Investigator)
timeFrame: Through substudy completion, an average of 2 years
Secondary outcomes:
measure: PFS per RECIST 1.1 as assessed by the Investigator
timeFrame: Through substudy completion, an average of 2 years
measure: OS
timeFrame: Through substudy completion, an average of 2 years
measure: other safety related endpoints
timeFrame: Through substudy completion, an average of 2 years
measure: DoR per RECIST 1.1 based on Investigator assessment.
timeFrame: Through substudy completion, an average of 2 years
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Baton Rouge
country: United States
facility: Research Site
state: Louisiana
city: Grand Rapids
country: United States
facility: Research Site
state: Michigan
city: Bronx
country: United States
facility: Research Site
state: New York
city: New Hyde Park
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: Shirley
country: United States
facility: Research Site
state: New York
city: Pittsburgh
country: United States
facility: Research Site
state: Pennsylvania
city: Beijing
country: China
facility: Research Site
city: Hangzhou
country: China
facility: Research Site
city: Hangzhou
country: China
facility: Research Site
city: Harbin
country: China
facility: Research Site
city: Hefei
country: China
facility: Research Site
city: Kunming
country: China
facility: Research Site
city: Wuhan
country: China
facility: Research Site
city: Yinchuan
country: China
facility: Research Site
city: Zhengzhou
country: China
facility: Research Site
city: Kashiwa
country: Japan
facility: Research Site
city: Sunto-gun
country: Japan
facility: Research Site
city: Tokyo
country: Japan
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: Elche(Alicante)
country: Spain
facility: Research Site
city: L'Hospitalet de Llobregat
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Santander
country: Spain
facility: Research Site
city: Hsinchu
country: Taiwan
facility: Research Site
city: Kaohsiung
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 City
country: Taiwan
facility: Research Site
city: Edinburgh
country: United Kingdom
facility: Research Site
city: Leeds
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Oxford
country: United Kingdom
facility: Research Site
Study officials:
References: