Esophageal Cancer Clinical Trials

• Capable of giving signed informed consent

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

• Previously untreated histologically documented unresectable, locally advanced, or metastatic gastric, GEJ, or distal esophagus (distal third of the esophagus) adenocarcinoma

• Positive CLDN18.2 expression, as determined prospectively by central IHC testing

• Confirmed PD-L1 CPS status by central IHC testing and ICI eligibility per investigator judgement is required to determine cohort eligibility as described below:

‣ Cohort 1: PD-L1 positive as determined by central IHC testing and the participant is deemed ICI eligible per investigator judgement.

⁃ Cohort 2: PD-L1 negative as determined by central IHC testing OR the participant is ICI ineligible

• ECOG performance status of 0 or 1 with no deterioration to \> 1 over the previous 2 weeks prior to baseline at screening and prior to randomisation.

• Minimum life expectancy of ≥ 12 weeks.

• At least one lesion (measurable and/or non-measurable) that can be accurately assessed by the investigator based on RECIST 1.1.

• Adequate organ and bone marrow function as specified in the protocol

• Body weight ≥ 35 kg.

• Sex and contraceptive requirements