• 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 with well documented Gilbert's syndrome; biliary drainage is allowed for biliary obstruction

• Serum creatinine \< 1.5 x ULN or creatinine clearance \>30 mL/min/1.73 m2

• Alanine aminotransferase (AST) and aspartate aminotransferase (ALT) \< 2.5x ULN within normal range or \< 5.0 x ULN if liver metastases are present

• If a female patient is of child-bearing potential, as evidenced by regular menstrual periods, she must have a negative pregnancy test (urine or serum; beta-human chorionic gonadotropin (β-hCG)) documented prior to the first administration of study drug. If sexually active, the patient must agree to use contraception considered adequate and appropriate by the Investigator during the period of administration of study drug and after the end of treatment as recommended.

• Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.