Establishment of Precision Targeted Therapy Strategies for Advanced Gastric Cancer Based on Novel Molecular Subtyping

NCT ID: NCT06881017

Last Updated: 2025-03-18

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 140 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-05-01
• Study Completion Date: 2029-11-01

Brief Summary

This study is a prospective, umbrella-design, Phase II clinical trial. Eligible participants with advanced or metastatic gastric cancer who are treatment-naïve for advanced-stage systemic therapy will undergo biomarker profiling (HER2, CLDN18.2, and PD-L1) via next-generation sequencing (NGS) or immunohistochemistry (IHC). Participants will be stratified into distinct molecular subtypes and assigned subtype-specific therapeutic regimens. The primary objectives are to assess treatment efficacy (e.g., objective response rate) and safety profiles across molecularly defined cohorts.

Conditions

Gastric Cancer; HER2 + Gastric Cancer; CLDN18.2-positive Adenocarcinoma of the Gastroesophageal Junction; PD-L1 Positive

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1

HER2(+)\&CLDN18.2(+)\&PD-L1(+)

Group Type: EXPERIMENTAL

Trastuzumab

Intervention Type: DRUG

iv，d1

Adebrelimab

Intervention Type: DRUG

iv，d1，q3w

S-1

Intervention Type: DRUG

po，bid，d1-14，q3w

zolbetuximab

Intervention Type: DRUG

iv，d1

SHR-A1904

Intervention Type: DRUG

iv，d1 ，q3w

Cohort 2

HER2(+)\&CLDN18.2(+)\&PD-L1(-)

Group Type: EXPERIMENTAL

Trastuzumab

Intervention Type: DRUG

iv，d1

S-1

Intervention Type: DRUG

po，bid，d1-14，q3w

SHR-A1904

Intervention Type: DRUG

iv，d1 ，q3w

Cohort 3

HER2(2+ or 3+)\&CLDN18.2(-)\&PD-L1(-)

Group Type: EXPERIMENTAL

S-1

Intervention Type: DRUG

po，bid，d1-14，q3w

SHR-A1811

Intervention Type: DRUG

iv，d1 ，q3w

Cohort 4

HER2(-)\&CLDN18.2(+)\&PD-L1(+)

Group Type: EXPERIMENTAL

Adebrelimab

Intervention Type: DRUG

iv，d1，q3w

S-1

Intervention Type: DRUG

po，bid，d1-14，q3w

SHR-A1904

Intervention Type: DRUG

iv，d1 ，q3w

Cohort 5

HER2(-)\&CLDN18.2(-)\&PD-L1(+)

Group Type: EXPERIMENTAL

Capecitabine

Intervention Type: DRUG

po，bid，d1-14

Oxaliplatin

Intervention Type: DRUG

iv，d1，q3w

SHR-1701

Intervention Type: DRUG

iv，d1 ，q3w

Cohort 6

HER2(-)\&CLDN18.2(+)\&PD-L1(-)

Group Type: EXPERIMENTAL

S-1

Intervention Type: DRUG

po，bid，d1-14，q3w

SHR-A1904

Intervention Type: DRUG

iv，d1 ，q3w

Cohort 7

HER2(-)\&CLDN18.2(-)\&PD-L1(-)

Group Type: EXPERIMENTAL

Apatinib

Intervention Type: DRUG

po，qd，d1-21，q3w

S-1

Intervention Type: DRUG

po，bid，d1-14，q3w

Oxaliplatin

Intervention Type: DRUG

iv，d1，q3w

Interventions

Trastuzumab

iv，d1

Intervention Type: DRUG

Adebrelimab

iv，d1，q3w

Intervention Type: DRUG

Apatinib

po，qd，d1-21，q3w

Intervention Type: DRUG

S-1

po，bid，d1-14，q3w

Intervention Type: DRUG

Capecitabine

po，bid，d1-14

Intervention Type: DRUG

Oxaliplatin

iv，d1，q3w

Intervention Type: DRUG

zolbetuximab

iv，d1

Intervention Type: DRUG

SHR-A1811

iv，d1 ，q3w

Intervention Type: DRUG

SHR-A1904

iv，d1 ，q3w

Intervention Type: DRUG

SHR-1701

iv，d1 ，q3w

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Age ≥18 years, regardless of gender;

2. Histologically or pathologically confirmed gastric adenocarcinoma or adenocarcinoma of the gastroesophageal junction;

3. Advanced or metastatic disease with no prior systemic therapy for advanced-stage disease (Patients who relapsed >6 months after completing neoadjuvant/adjuvant therapy are eligible, with prior neoadjuvant/adjuvant regimens not counted as prior lines of therapy);

4. At least one measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST v1.1);

5. Archival or fresh tumor tissue sample available for biomarker testing (HER2, CLDN18.2, and PD-L1 expression);

6. ECOG performance status: 0-1;

7. Life expectancy ≥12 weeks;

8. Adequate organ and bone marrow function meeting the following criteria:

1. Hemoglobin ≥90 g/L (no blood transfusion within 14 days);

2. Absolute neutrophil count (ANC) ≥1.5×10⁹/L;

3. Platelet count ≥90×10⁹/L;

4. Total bilirubin ≤1.5×upper limit of normal (ULN);

5. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN (≤5×ULN if liver metastases are present);

6. Serum creatinine ≤1.5×ULN;

7. Left ventricular ejection fraction (LVEF) ≥50% by echocardiography; QTc interval <450 ms for males and <470 ms for females;

9. Coagulation parameters:

10. For patients not on anticoagulation therapy: INR ≤1.5 and activated partial thromboplastin time (APTT) ≤1.5×ULN;

11. For patients receiving full-dose or parenteral anticoagulation: Stable anticoagulant dose for ≥2 weeks prior to enrollment, with coagulation tests within the therapeutic range;

12. Contraception requirements:

13. Women of childbearing potential must have a negative pregnancy test (serum or urine) within 14 days prior to enrollment and agree to use effective contraception during the study and for 3 months after the last dose;

14. Men must be surgically sterile or agree to use effective contraception during the study and for 3 months after the last dose;

15. Recovery from prior therapy-related toxicities to ≤Grade 1 (surgical wounds must be fully healed if applicable);

16. Voluntary participation with signed informed consent form and anticipated adherence to protocol requirements.

Exclusion Criteria

1. History of gastrointestinal perforation and/or fistula within 6 months prior to treatment, or active gastrointestinal bleeding within 3 months;

2. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage;

3. Known history of hypersensitivity to any component of the investigational drug(s) or excipients;

4. Prior treatments meeting any of the following:

1. Received any investigational drug within 4 weeks prior to the first dose of the study drug or within 5 half-lives of the last investigational agent (whichever is shorter);

2. Concurrent enrollment in another interventional clinical study (observational or follow-up studies are permitted);

3. Received antitumor therapy (including radiotherapy, chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologics, or tumor embolization) within 2 weeks prior to the first dose of the study drug;

5. History of leptomeningeal metastasis or current active brain metastases;

6. Severe infection (CTCAE v5.0 Grade >2) within 4 weeks prior to the first dose of the study drug (e.g., pneumonia requiring hospitalization, bacteremia, or septic complications); active pulmonary inflammation on baseline chest imaging, or signs/symptoms of infection requiring oral/IV antibiotics within 2 weeks prior to the first dose (prophylactic antibiotics excluded);

7. History of interstitial lung disease (except radiation pneumonitis without steroid treatment or non-infectious pneumonitis);

8. Active tuberculosis (TB) infection confirmed by medical history or CT scan, history of active TB within 1 year prior to enrollment, or untreated active TB diagnosed >1 year prior to enrollment;

9. Diagnosis of another malignancy within 5 years prior to the first dose of the study drug, except malignancies with low metastatic/lethal risk (5-year survival rate >90%), such as adequately treated basal cell carcinoma, squamous cell skin cancer, or carcinoma in situ of the cervix;

10. Pregnant or lactating women;

11. Other conditions deemed by the investigator to jeopardize subject safety or trial integrity, including severe comorbidities (e.g., psychiatric disorders), clinically significant laboratory abnormalities, or social/family factors that may compromise protocol adherence or data collection.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

China Medical University, China

OTHER

Sponsor Role: lead

Responsible Party

Xiujuan Qu

Director

Responsibility Role: PRINCIPAL_INVESTIGATOR

Other Identifiers

MA-GC-II-023

Identifier Type: -

Identifier Source: org_study_id