Adjuvant TRastuzumab Deruxtecan for HER2-positive Gastroesophageal Cancer With Persistence of miNImal Residual Disease

Inclusion Criteria of the Interventional TRINITY study: 1. Written informed consent and any locally required authorization (such as the European Union \[EU\] Data Privacy Directive) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations. 2. Compliance with all the study procedures and treatments. Patients must be accessible for treatment and follow-up. Patients registered on this trial must be treated and followed at the participating Centre. 3. Age ≥ 18 years old. 4. Eastern Cooperative Oncology group (ECOG) Performance Status 0-1. 5. Life expectancy of at least 12 weeks. 6. Resected gastric or gastroesophageal junction (Siewert I-II-III) cancer/esophageal adenocarcinoma, after the completion of pre-operative chemotherapy with FLOT, as per standard clinical practice. 7. Absence of distant metastases as defined by post-operative radiological assessments (contrast-enhanced CT scan of the thorax and abdomen or, in case of contraindications, non-contrast-enhanced chest CT scan and abdomen Magnetic Resonance Imaging) 8. Presence of locally determined HER2 overexpression/amplification on the post-treatment surgical tissue specimen defined as IHC 3+ or 2+/ISH amplified. 9. Positivity of the post-operative liquid biopsy, performed 2-6 weeks after the radical surgery. 10. LVEF ≥ 50% within 28 days before randomization/enrolment. 11. Adequate bone marrow and organ function within 14 days before randomization/enrolment as described below: 1. Neutrophil count ≥ 1.5 x 10\^3/μL 2. Platelet count ≥ 100 x 10\^6/μL 3. Haemoglobin ≥ 9 g/dL 4. Total bilirubin lower than 1.5 time the upper-normal limits (ULN) of the Institutional normal values 5. AST (SGOT) and/or ALT (SGPT) \<3 x ULN 6. serum albumin ≥ 2.5 g/dL 7. Creatinine clearance (calculated according to Cockroft and Gault) \> 60 mL/min 8. International normalised ratio or Prothrombin time and either partial thromboplastin or activated partial thromboplastin time ≤ 1.5 × ULN 12. Evidence of post-menopausal status or negative serum pregnancy test for females of childbearing potential who are sexually active with a non-sterilized male partner. For women of childbearing potential, a negative result for serum pregnancy test (test must have a sensitivity of at least 25 mIU/mL) must be available at the screening visit and urine beta-human chorionic gonadotropin (β-HCG) pregnancy test prior to each administration of IMP. Women of childbearing potential are defined as those who are not surgically sterile (i.e. underwent bilateral salpingectomy, bilateral oophorectomy, or complete hysterectomy) or post-menopausal. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. 13. Female patients of childbearing potential who are sexually active with a non-sterilized male partner must use at least one highly effective method of contraception, from the time of screening and must agree to continue using such precautions for 7 months after the last dose of IMP. Not all methods of contraception are highly effective. Female patients must refrain from breastfeeding while on study and for 7 months after the last dose of IMP. Complete heterosexual abstinence for the duration of the study and drug washout period is an acceptable contraceptive method if it is line with the patient's usual lifestyle (consideration must be made to the duration of the clinical trial); however, periodic or occasional abstinence, the rhythm method, and the withdrawal method are not acceptable. 14. Non-sterilized male patients who are sexually active with a female partner of childbearing potential must use a condom with spermicide from screening to 4 months after the final dose of IMP for T-DXd while 6 months for docetaxel and oxaliplatin. Complete heterosexual abstinence for the duration of the study and drug washout period is an acceptable contraceptive method if it is in line with the patient's usual lifestyle (consideration must be made to the duration of the clinical trial); however, periodic or occasional abstinence, the rhythm method, and the withdrawal method are not acceptable. It is strongly recommended for the female partners of a male patient to also use at least one highly effective method of contraception throughout this period. In addition, male patients should refrain from fathering a child, or freezing or donating sperm from the time of randomisation/enrolment, throughout the study and for 4 months after the last dose of IMP for T-DXd while 6 months for docetaxel and oxaliplatin. Preservation of sperm should be considered prior to enrollment in this study. 15. Female subjects must not donate, or retrieve for their own use, ova from the time of randomization/enrolmentand throughout the study treatment period, and for at least 7 months after the final study drug administration. They should refrain from breastfeeding throughout this time. Preservation of ova may be considered prior to enrollment in this study. Exclusion Criteria of the Interventional TRINITY study: 1. Involvement in the planning and/or conduct of the study (applies to both Investigator staff and/or staff at the study site) 2. Participation in another clinical study with an investigational product during the last 12 months 3. Signs of distant metastases at any site. 4. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, renal disease, neurological disease or peripheral neuropathy, serious chronic gastrointestinal conditions associated with diarrhea, or substance abuse or any other medical or psychiatric illness/social situations that in the opinion of the investigator would limit compliance with study requirement, interfere with the subject's participation in the clinical study, substantially