A Phase 1/2, Open-Label, Dose Escalation and Expansion Study with PT886 followed by a Multi-cohorT Study in Patients With Advanced GastrIc, Gastroesophageal JuNction (GEJ), and Pancreatic Ductal AdEnocarcinomas of PT886, in Combination with ChemotherAp…

Key Inclusion Criteria 1. 18 years or older and able to sign informed consent and comply with the protocol. 2. Measurable disease as defined by RECIST V1.1 criteria for solid tumors. 3. 3. Part A and Part B: Histologically or cytologically confirmed unresectable advanced or metastatic solid gastric, gastroesophageal junction (GEJ), or pancreatic tumors (adenocarcinomas type) previously treated for advanced (metastatic or unresectable) disease or for which treatment is not available or not tolerated. Part C, Cohort 1: 2L m/a GC/GEJ-C patients will receive PT886 in combination with Paclitaxel. Part C, Cohort 2: 1L m/a PDAC patients will receive PT886 in combination with Gemcitabine plus nab-Paclitaxel (Abraxane). Part C, Cohort 2b: 1L m/a PDAC patients will receive PT886 in combination with Gemcitabine plus FOLFIRINOX/mFFX. Part D, Cohort 3: 2L or 3L m/a GC/GEJ-C patients will receive PT886 in combination with KEYTRUDA® (pembrolizumab). Part D, Cohort 4: 1L HER2 negative m/a GC/GEJ-C patients will receive PT886 in combination with SOC chemotherapy and KEYTRUDA® (pembrolizumab). Part D, Cohort 5: Patients with m/a GC/GEJ-C, that have progressed under 1L SOC chemotherapy, and zolbetuximab, will receive PT886 in combination with KEYTRUDA® (pembrolizumab). 4. Biopsies: Able to provide a formalin fixed, paraffin embedded (FFPE) tumor tissue sample (preferably fresh biopsy or if not possible, archival tissue) to be assessed for CLDN18.2 expression and other biomarkers. Biopsy must be excisional, incisional, or core needle. This biopsy may not be done if the biopsy poses a risk to the patient and/or per the Investigators discretion. Parts B, C and D: Patients must present with ≥ 50%; ≥ 2+ (Part B) or ≥ 10%; ≥ 2+ (Parts C and D) CLDN18.2 positive TC in their tumor tissue. 5. ECOG performance status of 0 or 1. 6. Adequate organ function confirmed at screening and within 96 hours of initiating treatment. Key Exclusion Criteria Patients are excluded from the study if any of the following criteria apply: 1. Women who are pregnant or lactating. 2. Women of child-bearing potential (WOCBP) who do not use adequate birth control. 3. Has an active autoimmune disease that has required systemic treatment in the past 2 years. 4. Condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days prior to study treatment. 5. Patients with a history of (non-infectious) pneumonitis that required steroids, current pneumonitis, or have a history of interstitial lung disease. History of COVID-19 pneumonia with fibrotic changes. 6. Patients with untreated brain or central nervous system (CNS) metastases or brain/CNS metastases that have progressed (e.g., evidence of new or enlarging brain metastasis or new neurological symptoms attributable to brain/CNS metastases). 7. Prior CLDN18.2 or CD47 targeting therapies, or SIRPα (signal regulatory protein alpha) targeting agents. For Part D, Cohort 5, prior treatment with zolbetuximab is allowed. 8. Impaired cardiac function or significant diseases. 9. Prior hemolytic anemia or Evans Syndrome in the last 3 months. 10. Active gastric perforation, pyloric obstruction, complete biliary obstruction, complete or incomplete intestinal obstruction requiring clinical intervention, or pleural effusion or peritoneal effusion requiring clinical intervention. 11. Patients who have experienced any thromboembolic event such as deep vein thrombosis (DVT) or pulmonary embolism in the past 6 months. Additional inclusion and exclusion criteria will apply.