Spevatamig (PT886) as Monotherapy or in Combination With Chemo and/or ICI, for the Treatment of Patients With Advanced Gastric, Gastroesophageal Junction, Pancreatic Ductal or Biliary Tract Carcinomas (the TWINPEAK Study)

Inclusion Criteria

• 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), biliary tract or pancreatic carcinomas previously treated for advanced (metastatic or unresectable) disease or for which treatment is not available or not tolerated. Part C, Cohort C1: 2L m/a GC/GEJ-C patients will receive Spevatamig (PT886) in combination with Paclitaxel. Patients who are HER2 positive are eligible. Part C, Cohort C2: 1L m/a PDAC patients will receive Spevatamig (PT886) in combination with Gemcitabine plus nab-Paclitaxel (Abraxane). Part C, Cohort C3: 1L m/a PDAC patients will receive Spevatamig (PT886) in combination with Gemcitabine plus FOLFIRINOX/mFFX. Cohort C4: Patients with m/a BTC who have progressed on 1L SOC chemotherapy (GemCis) ± ICI and are eligible for 2L SOC FOLFOX treatment. Cohort C5: Patients with m/a HER2 negative GC/GEJC and present a PD-L1 CPS score of <1%, who are treatment naïve for their m/a disease and eligible for treatment with SOC chemotherapy (mFOLFOX6 or CAPOX). Part D, Cohort D2: Patients with m/a GC/GEJ-C, that have progressed under 1L SOC chemotherapy, and zolbetuximab, will receive Spevatamig (PT886) in combination with KEYTRUDA® (pembrolizumab). Part D, Cohort D3: 2L or 3L m/a GC/GEJ-C patients will receive Spevatamig (PT886) in combination with KEYTRUDA® (pembrolizumab). Part D, Cohort D4: 1L HER2 negative m/a GC/GEJ-C patients will receive Spevatamig (PT886) in combination with SOC chemotherapy and 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. Parts C and D: Patients must present with ≥ 10%; ≥ 2+ 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 72 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 D2, 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.