An Open-label Study to Investigate the Efficacy and Safety of Dato-DXd + Rilvegostomig vs SoC in Adult Participants With High-risk MIUC

Inclusion criteria: 1. Participant must be \> 18 years of age at the time of signing the ICF. 2. Histologically confirmed MIUC of the bladder or upper tract. 3. Completed R0 radical resection 28 to 120 days before randomisation, with negative margins and no residual or metastatic disease. 4. Pathologic evidence of urothelial carcinoma at high-risk of recurrence and 1. not received neoadjuvant therapy and has pT3-pT4aN0, or any pT with pN+ stage 2. completed neoadjuvant treatment and has ypT2-ypT4a, or any ypT with ypN+ stage 5. No evidence of disease at screening, 6. ECOG performance status of 0 or 1 with no deterioration over the previous 2 weeks prior to randomisation. 7. Minimum life expectancy of \> 12 weeks at time of screening. 8. An archival surgical tumour sample must be available pre-randomisation for central testing. 9. Adequate organ and bone marrow function within 28 days before randomisation. Exclusion criteria: 1. Any tumour with predominant or pure high grade neuroendocrine carcinoma component. 2. Partial cystectomy in the setting of bladder cancer primary tumour or partial nephrectomy. 3. Any adjuvant systemic or radiation therapy post-surgery for urothelial carcinoma. 4. Severe or uncontrolled systemic diseases, history of organ transplant or allogeneic stem cell transplant, or psychological disorders/social situations, and/or substance abuse. 5. History of clinically significant corneal disease. 6. History of another primary malignancy except for malignancy treated with curative intent with no known active disease within 2 years before the first dose of study intervention and of low potential risk for recurrence. 7. Ongoing toxicities except alopecia from prior cancer treatment must be Grade ≤ 1 or at baseline. Stable Grade 2 toxicities are allowed if unchanged for ≥3 months and managed by standard care. 8. Active or uncontrolled hepatitis B or C virus infection. 9. Known HIV infection that is not well controlled. 10. Any other active or uncontrolled infection including tuberculosis requiring systemic treatment that has not resolved by the time of randomisation. 11. History of non-infectious ILD/pneumonitis including radiation, pneumonitis that required steroids, has current ILD/pneumonitis, or has suspected ILD/pneumonitis that cannot be ruled out by imaging at screening. 12. Has clinically severe pulmonary function compromise. 13. Mean resting corrected QTcF \> 470 ms regardless of gender, obtained from triplicate 12-lead ECGs performed at screening 14. Uncontrolled or significant cardiac conditions. 15. Active or prior documented autoimmune or inflammatory disorders requiring systemic treatment in the past 5 years. 16. Prior exposure to TROP2-directed therapies, other ADCs with deruxtecan, therapeutic anti-cancer vaccines, anti-TIGIT therapy or any other anti-cancer therapy targeting immune-regulatory receptors or mechanisms. 17. Current or prior use of immunosuppressive medication within 14 days prior to treatment assignment/randomisation. 18. Known history of severe hypersensitivity reactions to any study drug 19. Not eligible to receive at least one of SoC according to local regulations/approvals. 20. Currently pregnant (confirmed with positive pregnancy test), breastfeeding or planning to become pregnant.