AZD0901 Compared With Investigator's Choice of Therapy in Participants With Second- or Later-line Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma Expressing Claudin18.2

Capable of giving signed informed consent prior to any study procedure.

Participant must be at least 18 years or the legal age of consent in the jurisdiction in which the study is taking place at the time of signing the ICF.

Histologically confirmed unresectable, locally advanced or metastatic adenocarcinoma of gastric, GEJ, or distal esophagus (distal third of the esophagus) and the following requirement:

(a) Participants with positive CLDN18.2 expression from archival tumor collected within past 24 months or from a fresh biopsy.

Disease progression on or after at least one prior line of treatment (LoT) for advanced or metastatic disease, which included a fluoropyrimidine and a platinum, for advanced or metastatic disease.

Must have at least one measurable or evaluable lesion assessed by the Investigator based on RECIST 1.1.

ECOG performance status of 0 or 1 with no deterioration over the previous 2 weeks prior to baseline or day of first dosing.

Predicted life expectancy of ≥ 12 weeks.

Adequate organ and bone marrow function

Body weight of ≥ 35 kg.

Sex and Contraceptive Requirements

Participants with known HER2 positive status as defined as IHC 3+ or IHC 2+/ISH + (Cases with HER2: CEP17 ratio ≥ 2 or an average HER2 copy number ≥ 6.0 signals/cell are considered positive by ISH). Participants must undergo local (or have had) HER2 testing by IHC/ISH, and the most recent result of HER2 status will be used to determine the eligibility.

Participant has significant or unstable gastric bleeding and/or untreated gastric ulcers.

CNS metastases or CNS pathology including: epilepsy, seizures or aphasia within 3 months prior to consent, severe brain injury, dementia, Parkinson's disease, neurodegenerative diseases, cerebellar disease, severe uncontrolled mental illness, psychosis, CNS involvement of autoimmune diseases.

Participant has known clinically significant corneal disease (eg, active keratitis or corneal ulcerations).

Persistent toxicities (CTCAE Grade ≥ 2) caused by previous anticancer therapy, excluding alopecia. Participants with irreversible toxicity that is not reasonably expected to be exacerbated by study intervention may be included (eg, hearing loss).

Prior exposure to any ADC with MMAE payload or any CLDN18.2 targeting treatment other than naked monoclonal antibody (eg, CLDN18.2 targeting CAR-T cell therapy, multi-specific antibody including targeting CLDN18.2, etc).

History of thromboembolic events:

1. Participants with venous thromboembolism within the past 6 months prior to randomization: participants with venous port or catheter thrombosis or superficial venous thrombus that do not require treatment or are stable on treatment with anticoagulants are excepted
2. History of arterial thromboembolism within the past 12 months prior to randomization

As judged by the Investigator, any evidence of diseases which in the Investigator's opinion, makes it undesirable for the participant to participate in the study or that would jeopardize compliance with the protocol.