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

What this study is about

Purpose: to assess efficacy and safety of Dato-DXd + rilvegostomig as adjuvant therapy versus SoC in MIUC participants with high-risk residual disease after radical resection. Study details: Duration: \~78 months (6.5 years) from FSI to last subject visit Treatment length: up to \~12 months, depending on randomized arm Visit frequency: every 3 weeks in Arms 1 and 2; every 2-4 weeks per SoC in Arm 3

Who can join (things the study team will check)

✅ You may be able to join if…

• Participant must be > 18 years of age at the time of signing the ICF.
• Histologically confirmed MIUC of the bladder or upper tract.
• Completed R0 radical resection 28 to 120 days before randomisation, with negative margins and no residual or metastatic disease.
• Pathologic evidence of urothelial carcinoma at high-risk of recurrence and
  • not received neoadjuvant therapy and has pT3-pT4aN0, or any pT with pN+ stage
  • completed neoadjuvant treatment and has ypT2-ypT4a, or any ypT with ypN+ stage
• No evidence of disease at screening,
• ECOG performance status of 0 or 1 with no deterioration over the previous 2 weeks prior to randomisation.
• Minimum life expectancy of > 12 weeks at time of screening.
• An archival surgical tumour sample must be available pre-randomisation for central testing.
• Adequate organ and bone marrow function within 28 days before randomisation.

🚫 You may not be able to join if…

• Any tumour with predominant or pure high grade neuroendocrine carcinoma component.
• Partial cystectomy in the setting of bladder cancer primary tumour or partial nephrectomy.
• Any adjuvant systemic or radiation therapy post-surgery for urothelial carcinoma.
• Severe or uncontrolled systemic diseases, history of organ transplant or allogeneic stem cell transplant, or psychological disorders/social situations, and/or substance abuse.
• History of clinically significant corneal disease.
• 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.
• 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.
• Active or uncontrolled hepatitis B or C virus infection.
• Known HIV infection that is not well controlled.
• Any other active or uncontrolled infection including tuberculosis requiring systemic treatment that has not resolved by the time of randomisation.
• 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.
• Has clinically severe pulmonary function compromise.
• Mean resting corrected QTcF > 470 ms regardless of gender, obtained from triplicate 12-lead ECGs performed at screening
• Uncontrolled or significant cardiac conditions.
• Active or prior documented autoimmune or inflammatory disorders requiring systemic treatment in the past 5 years.
• 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.
• Current or prior use of immunosuppressive medication within 14 days prior to treatment assignment/randomisation.
• Known history of severe hypersensitivity reactions to any study drug
• Not eligible to receive at least one of SoC according to local regulations/approvals.
• Currently pregnant (confirmed with positive pregnancy test), breastfeeding or planning to become pregnant.

Where this trial is running

• Research Site, Hot Springs, Arkansas, United States
• Research Site, Little Rock, Arkansas, United States
• Research Site, Little Rock, Arkansas, United States
• Research Site, San Francisco, California, United States
• Research Site, Chicago, Illinois, United States
• Research Site, Boston, Massachusetts, United States
• Research Site, Kansas City, Missouri, United States
• Research Site, Lincoln, Nebraska, United States
• Research Site, Omaha, Nebraska, United States
• Research Site, Albany, New York, United States
• Research Site, New York, New York, United States
• Research Site, Cleveland, Ohio, United States

+ 148 more sites.

Who to contact

AstraZeneca Clinical Study Information Center · 1-877-240-9479 · information.center@astrazeneca.com

It's completely normal to call and ask questions before deciding anything. Mention the study ID: NCT07720284.