A Phase III, Open-Label, Randomised, Multicentre, Global Study of Adjuvant Datopotamab Deruxtecan in Combination With Rilvegostomig in Participants With High-risk Muscle Invasive Urothelial Carcinoma

Study Identifier:
D763TC00001
CT.gov Identifier:
NCT07720284
EudraCT Identifier:
202552503057
EU Trial (CTIS) Number:
N/A
Study Contact Information:
(210) 593-5651 or [email protected]
Will Be Recruiting

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Study Summary

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

In participants identified as high-risk during radical resection, the efficacy and safety of Dato-DXd combined with rilvegostomig as adjuvant therapy compared to SoC were evaluated.

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. (TROPION-Urothelial04)

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
Bladder
Renal
Phase
The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
Phase III
Sex
Female & Male
Age
18+ years
Study Drug
N/A
Study Status
Indicates the current recruitment status or the expanded access status
Will Be Recruiting

Requirements information
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. Participants must be 18 years of Age or older when signing up for the ICF.
  • MIUC of the bladder or upper urinary tract confirmed by histology.
  • Radical (R0) surgical resection was performed between 28 and 120 days prior to Allocation. There was no invasive tumor at the surgical margins. There was no evidence of residual tumor or metastasis postoperatively.
  • All participants must have pathological evidence of urothelial carcinoma (originating from the bladder, ureter, or renal pelvis) with a high risk of recurrence: (a) If they have not received neoadjuvant therapy, the postoperative pathological stage must be any pT3-pT4aN0 or any pT with pN+. (b) If they have completed neoadjuvant therapy, the postoperative pathological stage must be any ypT2-ypT4a or any ypT with ypN+.
  • All participants must be free of disease at the time of screening.
  • An ECOG PS score of 0 or 1 indicates no deterioration within the two weeks prior to Allocation.
  • During the screening period, the participants' shortest life expectancy was >12 weeks.
  • Before Allocation, existing archived surgically removed tumor samples must be provided and sent to the central laboratory.
  • Organ and bone marrow function were normal within 28 days prior to Allocation.
  • 1. Participant must be 18 years of age or older 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
  • - 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
  • 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. An archival surgical tumour sample must be available pre-randomisation for central testing.
  • 8. 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. Exclude any tumors that are primarily composed of high-grade neuroendocrine carcinoma or are entirely composed of high-grade neuroendocrine carcinoma.
  • Patients who have undergone partial cystectomy for primary bladder cancer or partial nephrectomy for primary renal pelvis tumors.
  • The patient has previously received any postoperative adjuvant systemic therapy or radiotherapy for urothelial carcinoma.
  • Serious or uncontrolled systemic diseases, history of organ transplantation or allogeneic stem cell transplantation, or mental disorder/social abnormality, and/or substance abuse.
  • Any history of clinically significant corneal disease.
  • Other primary malignant tumor history, except for the following: radical malignant tumor, no known active disease and low potential risk of recurrence within 2 years prior to the first dose of study intervention.
  • Persistent toxicities (excluding hair loss) caused by previous anti-tumor therapy or radical surgery that have not improved to grade ≤1 or baseline levels are eligible for enrollment in the study. Participants with stable grade 2 toxicities (defined as those that have not worsened to grade >2 within at least 3 months prior to the first dose of the study intervention and are manageable with SoC therapy) are eligible for enrollment in the study.
  • Having active or uncontrolled hepatitis B or hepatitis C virus infection.
  • Poorly controlled HIV infection is known.
  • Allocation if there are any other active or uncontrolled infections that have not yet subsided and require systemic treatment, including tuberculosis infection.
  • Those with a history of non-infectious ILD/non-infectious pneumonia (including radiation pneumonitis) requiring corticosteroid treatment, or drug-induced ILD/non-infectious pneumonia, currently having ILD/non-infectious pneumonia, or whose imaging examinations at the time of screening could not rule out suspected ILD/non-infectious pneumonia.
  • There is clinically significant severe lung function impairment due to pulmonary complications.
  • Three repeated 12-lead ECGs during the screening period showed a QT interval >470ms, regardless of Gender.
  • Suffering from uncontrolled or significant heart disease.
  • Having an active or previously diagnosed autoimmune or inflammatory disease requiring systemic treatment within the past 5 years.
  • Previous treatments include: (a) TROP2-targeting therapy; (b) other ADCs with deruxtecan payloads; (c) therapeutic anti-tumor vaccines; and (d) anti-TIGIT therapy or any other anti-tumor therapy targeting immunomodulatory receptors or mechanisms.
  • Currently or previously used immunosuppressive drugs within 14 days prior to treatment allocation/ Allocation.
  • Participants with a known history of severe hypersensitivity to any investigational drug.
  • According to local regulations/approvals, at least one SoC is not eligible for acceptance.
  • For women only: those who are pregnant (confirmed by a positive serum pregnancy test), breastfeeding, or planning to become pregnant.
  • 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 lower or at baseline. Stable Grade 2 toxicities are allowed if unchanged for at least 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 exceeding 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.

Clinical Study Information for Healthcare Providers

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Study Locations

Location
Investigator
Status
Condition(s) Treated at Site
Location
START Carolinas
Myrtle Beach, SC, United States, 29572
Investigator
Neal Shore
Status
Will Be Recruiting
Condition(s) Treated at Site
Bladder
Renal