Anti-PD-1 and CapOx for the First-line Treatment of dMMR Esophagogastric Cancer (AuspiCiOus)

Inclusion Criteria: * Patients must provide written informed consent according to ICH/GCP, and national/local regulations prior to any screening procedures. * Male or female adult patients (≥ 18 years). * Patients with histologically confirmed diagnosis of metastatic or irresectable HER2 negative adenocarcinoma of the stomach or gastroesophageal junction (Siewert II and III); patients with HER2 positive disease are eligible when treatment with trastuzumab is contraindicated. If histology cannot be obtained, cytology is acceptable to prove metastatic disease. * Patients with metastatic or irresectable adenocarcinoma of the stomach or oesophagus not pre-treated with chemotherapy or radiotherapy for irresectable or metastatic disease. Palliative radiotherapy on the primary tumor or a metastatic lesion is allowed if other untreated lesions eligible for evaluation are present. * Measurable disease as assessed by RECIST 1.1 * dMMR identified by IHC of mismatch repair proteins MLH1, PMS2, MSH2 en MSH6 * Primary tumor or metastasis accessible for repeat fresh histological biopsies * ECOG (WHO) performance status 0-2 * Patient has adequate bone marrow and organ function as defined by the following laboratory values: * Absolute Neutrophil Count (ANC) \> 1.5 x 109 /L * Hemoglobin (Hgb) \> 5.6 mmol/L * Platelets \> 100 x 109 /L * Serum total bilirubin within ≤ 1.5 x ULN (upper limit of normal); or total bilirubin \< 3.0 x ULN with direct bilirubin within normal range in patients …