A Study of ATG-022 Compared With Investigator's Choice of Treatment in Claudin 18.2-Positive Advanced Gastric or Gastroesophageal Junction Adenocarcinoma

A Randomized, Controlled, Open-label, Multicenter Phase III Study to Evaluate the Efficacy and Safety of ATG-022 Compared With Investigator's Choice of Treatment in Subjects With Claudin18.2-Positive Advanced Gastric or Gastroesophageal Junction Adenocarcinoma

This is a randomized, controlled, open-label, multicenter Phase III study to evaluate the efficacy and safety of ATG-022 compared with Investigator's Choice in participants with CLDN18.2-positive advanced gastric or gastroesophageal junction adenocarcinoma.

This study is based on the positive data for ATG-022 monotherapy in CLDN18.2-positive advanced gastric/GEJ adenocarcinoma obtained from the CLINCH study. Through PopPK and exposure-response (E-R) analysis of ATG-022, this study will use ATG-022 monotherapy at 1.8 mg/kg compared to Investigator's Choice to evaluate the efficacy and safety of the two treatment regimens in participants with advanced gastric/GEJ adenocarcinoma who have received prior second-line systemic therapy. The Investigator's Choice regimen includes two optional drugs: Docetaxel or Irinotecan. Both docetaxel and irinotecan are commonly used single-agent chemotherapy drugs in third-line treatment for gastric cancer.

Inclusion Criteria:

1. Provide signed and dated written informed consent (ICF) before any study-specific procedures, sampling, and analyses.

2. Age ≥ 18 years at the time of consent.

3. Histologically or cytologically confirmed unresectable locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma with positive CLDN18.2 expression.

4. Disease progression after at least second-line and no more than fourth-line systemic therapy. Prior therapy must have included a fluoropyrimidine and a platinum agent.

5. If archival tumor tissue sample obtained within 36 months prior to study participation is not available, participants should be willing to undergo a biopsy at screening.

6. Life expectancy of at least 12 weeks.

7. ECOG performance status of 0 or 1 at the time of ICF signing.

8. Adequate organ function, as evidenced by the following laboratory values (transfusion and hematopoietic growth factors are not permitted within 14 days before obtaining these laboratory values):

   1. ANC ≥ 1.5 × 10⁹/L.
   2. Platelet count ≥ 100 × 10⁹/L.
   3. Hemoglobin ≥ 90 g/L.
   4. ALT ≤ 2.5 × ULN, or ALT ≤ 5 × ULN in the presence of liver metastases.
   5. AST ≤ 2.5 × ULN, or AST ≤ 5 × ULN in the presence of liver metastases.
   6. Total bilirubin ≤ 1.5 × ULN.
   7. Creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 50 mL/min (measured or calculated per Cockcroft and Gault formula); confirmation of creatinine clearance is only required when creatinine ≥ 1.5 × ULN.
   8. Coagulation: INR or PT ≤ 1.5 × ULN. aPTT ≤ 1.5 × ULN (if participant is receiving anticoagulants, the value must be within the therapeutic range for the participant's condition).

9. Males of reproductive potential and females of childbearing potential must agree to use effective contraception from the time of ICF signing until 180 days after the last dose of study drug.

Exclusion Criteria:

1. Known active CNS metastases and/or carcinomatous meningitis.
2. Prior treatment with CLDN18.2-targeted therapy or cell therapy, excluding CLDN18.2 monospecific monoclonal antibodies.
3. Prior treatment with any chemotherapy, immunotherapy, anti-cancer drugs, or investigational products from previous clinical studies within 28 days prior to randomization, or within the period required for the investigational product or systemic anti-cancer treatment to be cleared from the body (e.g., 5 "half-lives"), whichever is deemed most appropriate by the Investigator.
4. Received extensive radiotherapy within 28 days prior to randomization, or limited-field radiotherapy for palliative purposes within 14 days prior to the first dose of study treatment.
5. Major surgery within 28 days prior to randomization (excluding placement of vascular access) or minor surgical procedures ≤ 7 days. No waiting period is required after port-a-cath placement and drain insertion.
6. Active autoimmune disease requiring systemic treatment
7. Presence of any severe or uncontrolled systemic disease as judged by the Investigator
8. Complications or other conditions (psychological, family, social, or geographical, etc.) that, in the Investigator's opinion, could affect compliance with the protocol or make the participant unsuitable for the study.