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

NCT06881017 | Not Yet Recruiting Phase 2

• 1 other identifier: MA-GC-II-023
• Study Type: interventional
• Target: 140
• Locations: 0 countries
• Sites: N/A

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

Keywords

gastric cancer; HER2; CLDN18.2; PD-L1

Outcome Measures

Primary Outcomes (1)

• ORR

  Objective Response Rate (ORR) is defined as the proportion of patients who achieve a complete response (CR) or partial response (PR) to a therapeutic intervention, as assessed by standardized criteria (e.g., RECIST 1.1 for solid tumors). It serves as a key efficacy endpoint in early-phase clinical trials to evaluate the preliminary antitumor activity of investigational therapies.

  2year

Secondary Outcomes (1)

• OS

  2year

Study Arms (7)

Cohort 1

EXPERIMENTAL

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

Drug: Trastuzumab; Drug: Adebrelimab; Drug: S-1; Drug: zolbetuximab; Drug: SHR-A1904

Cohort 2

EXPERIMENTAL

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

Drug: Trastuzumab; Drug: S-1; Drug: SHR-A1904

Cohort 3

EXPERIMENTAL

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

Drug: S-1; Drug: SHR-A1811

Cohort 4

EXPERIMENTAL

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

Drug: Adebrelimab; Drug: S-1; Drug: SHR-A1904

Cohort 5

EXPERIMENTAL

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

Drug: Capecitabine; Drug: Oxaliplatin; Drug: SHR-1701

Cohort 6

EXPERIMENTAL

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

Drug: S-1; Drug: SHR-A1904

Cohort 7

EXPERIMENTAL

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

Drug: Apatinib; Drug: S-1; Drug: Oxaliplatin

Interventions

Trastuzumab DRUG

iv，d1

Cohort 1; Cohort 2

Adebrelimab DRUG

iv，d1，q3w

Cohort 1; Cohort 4

Apatinib DRUG

po，qd，d1-21，q3w

Cohort 7

S-1 DRUG

po，bid，d1-14，q3w

Cohort 1; Cohort 2; Cohort 3; Cohort 4; Cohort 6; Cohort 7

Capecitabine DRUG

po，bid，d1-14

Cohort 5

Oxaliplatin DRUG

iv，d1，q3w

Cohort 5; Cohort 7

zolbetuximab DRUG

iv，d1

Cohort 1

SHR-A1811 DRUG

iv，d1 ，q3w

Cohort 3

SHR-A1904 DRUG

iv，d1 ，q3w

Cohort 1; Cohort 2; Cohort 4; Cohort 6

SHR-1701 DRUG

iv，d1 ，q3w

Cohort 5

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years, regardless of gender;
• Histologically or pathologically confirmed gastric adenocarcinoma or adenocarcinoma of the gastroesophageal junction;
• 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);
• At least one measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST v1.1);
• Archival or fresh tumor tissue sample available for biomarker testing (HER2, CLDN18.2, and PD-L1 expression);
• ECOG performance status: 0-1;
• Life expectancy ≥12 weeks;
• Adequate organ and bone marrow function meeting the following criteria:
• Hemoglobin ≥90 g/L (no blood transfusion within 14 days);
• Absolute neutrophil count (ANC) ≥1.5×10⁹/L;
• Platelet count ≥90×10⁹/L;
• Total bilirubin ≤1.5×upper limit of normal (ULN);
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN (≤5×ULN if liver metastases are present);
• Serum creatinine ≤1.5×ULN;
• Left ventricular ejection fraction (LVEF) ≥50% by echocardiography; QTc interval \<450 ms for males and \<470 ms for females;

You may not qualify if:

• History of gastrointestinal perforation and/or fistula within 6 months prior to treatment, or active gastrointestinal bleeding within 3 months;
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage;
• Known history of hypersensitivity to any component of the investigational drug(s) or excipients;
• Prior treatments meeting any of the following:
• 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);
• Concurrent enrollment in another interventional clinical study (observational or follow-up studies are permitted);
• 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;
• History of leptomeningeal metastasis or current active brain metastases;
• 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);
• History of interstitial lung disease (except radiation pneumonitis without steroid treatment or non-infectious pneumonitis);
• 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;
• 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;
• Pregnant or lactating women;
• 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.

Sponsors & Collaborators

• China Medical University, China: lead

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

Trastuzumab; apatinib; S 1 (combination); Capecitabine; Oxaliplatin; zolbetuximab; SHR-1701

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Coordination Complexes; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director

Study Record Dates

• First Submitted: March 9, 2025
• First Posted: March 18, 2025
• Study Start: May 1, 2025
• Primary Completion (Estimated): August 1, 2029
• Study Completion (Estimated): November 1, 2029
• Last Updated: March 18, 2025

Record last verified: 2025-03