This is a global, multicenter, randomized, open-label, Phase 2/3 study of Dato-DXd plus carboplatin or cisplatin versus gemcitabine plus carboplatin or cisplatin in participants with la/mUC who progressed during or after EV plus pembrolizumab combination treatment.
This trial will start with part A, Phase 2. During part A, Phase 2, preliminary efficacy and safety will be assessed, and the recommended Phase 3 dose (RP3D) will be identified when the data allow sufficient assessment of activity, safety, and tolerability. The Phase 3 part will start contingent upon the assessment in the Phase 2 part, taking into consideration the totality of information.
Adult ≥18 years at the time the ICF is signed (if the legal age of consent is > 18 years old, then follow the local regulatory requirements).
Histologically or cytologically confirmed unresectable locally advanced (T4b, any N; or any T, N 2-3) or metastatic (any T, any N, M1) urothelial carcinoma of the bladder, renal pelvis, ureter, or urethra.
Participant does not have radiological metastasis of a proven prostate cancer.
Increase in PSA within 2 consecutive measurements separated by at least 1 week (completed within 4 weeks prior to consent or within Screening) and neither of the measurements with an absolute value above 2 ng/mL.
Has had prior systemic therapy other than the combination of EV and pembrolizumab for la/mUC. The following participants may be considered eligible after approval by the Sponsor's Medical Monitor or Sponsor's designee.
History of an allogeneic bone marrow or solid organ transplant.
Concomitant treatment with any prohibited medications in this protocol.
Prior TROP2 directed ADC therapy.
Sequential
Dato-DXd
DrugDato-DXd will be administered as an intravenous (IV) infusion every three weeks (Q3W) at a dose of 4 mg/kg or 6 mg/kg in Part A or RP3D in Part B
Carboplatin
DrugCarboplatin will be administered as an intravenous (IV) infusion every three weeks (Q3W) at a dose of AUC 4.5 or 5.0 mg•min/mL
Cisplatin
DrugCisplatin will be administered as an intravenous (IV) infusion every three weeks (Q3W) at a dose of 70 mg/m2
Gemcitabine
DrugGemcitabine will be administered as an IV infusion at a dose of 1000 mg/m2 on Day 1 and 8 of every 3 week cycle.
Overall Response Rate - Part A (Phase 2)
Overall Response Rate (ORR) is defined as the proportion of participants with a Best Overall Response (BOR) of confirmed Complete Response (CR) or confirmed Partial Response (PR). As assessed by investigator per RECIST v1.1
Progression Free Survival as Assessed by Blinded Independent Central Review (BICR) - Part B (Phase 3)
Progression Free Survival (PFS) is defined as the time from randomization to the first documented radiographic disease progression or death due to any cause, whichever occurs first. As assessed by BICR per RECIST v1.1
Overall Survival - Part B (Phase 3)
Overall Survival (OS) is defined as the time from randomization to death due to any cause.
Duration of Response - Part A (Phase 2)
Duration of Response (DoR) is defined as the time from the date of first documentation of objective tumor response (confirmed CR or confirmed PR) to the date of the first documented radiographic disease progression or death due to any cause, whichever occurs first in responding participants. As assessed by investigator per RECIST v1.1
Progression Free Survival as Assessed by Investigator - Part B (Phase 3)
PFS is defined as the time interval from the date of randomization to the first documented radiographic disease progression or death due to any cause, whichever occurs first. As assessed by investigator per RECIST v1.1
Overall Response Rate - Part B (Phase 3)
ORR is defined as the proportion of participants with a BOR of confirmed CR or confirmed PR. As assessed by BICR and investigator per RECIST V1.1
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Daiichi Sankyo
Lead sponsor
AstraZeneca
Collaborator
