Clarity- PT01: This study is assessing how safe, tolerable and effective a medicine called AZD0901 is when given by itself and in combination with other treatments in people with locally advanced or metastatic cancer of the stomach, gastro-oesophageal junction or pancreas that express CLDN18.2A Phase II, Open-label, Multi-centre Study to Evaluate Safety, Tolerability, Efficacy, PK, and Immunogenicity of AZD0901 as Monotherapy and in Combination With Anti-cancer Agents in Participants With Advanced Solid Tumours Expressing Claudin 18.2.

Exclusion

Master Exclusion Criteria applicable to both sub studies:

• Unstable or active peptic ulcer disease or digestive tract bleeding including but not limited to clinically significant bleeding in the setting of prior CLDN18.2 directed therapy.
• Participants with clinically significant ascites that require drainage.
• A history of drug-induced non-infectious ILD/pneumonitis.
• Central nervous system metastases or CNS pathology.
• Peripheral neuropathy ≥ Grade 2 at screening.
• History of another primary malignancy.
• Prior exposure to any MMAE-based ADC.
• Prior exposure to any CLDN18.2 targeted agents except anti-CLDN18.2 monoclonal antibody.

Sub study 1 Specific Exclusion criteria:

• Participants with HER2-positive (3+ by IHC, or 2+ by IHC, and positive by ISH) or indeterminate GC/GEJC.
• Any factors that increase the risk of QTc prolongation or risk of arrhythmic events.
• The use of concomitant medications known to prolong the QT/QTc interval.

Sub study 2 Specific Exclusion criteria:

• Known DPD enzyme deficiency based on local testing where testing is SoC.
• Use of strong inhibitor or inducer of UGT1A1.
• Use of strong inhibitors or inducers of CYP3A4.