Dato-DXd plus Carboplatin or Cisplatin versus Gemcitabine plus Carboplatin or Cisplatin in Previously Treated la/mUC.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Daiichi Sankyo Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

28 Nov 2025 → ongoing

Decision date (initial)

2025-10-20

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Daiichi Sankyo Inc.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Others, Dose response, Pharmacodynamic, Pharmacokinetic, Safety

Phase 2:
• To evaluate the relative efficacy of Dato-DXd 4 mg/kg plus platinum therapy and Dato-DXd 6 mg/kg plus platinum therapy as measured by overall response rate (ORR) by investigator.

Phase 3:
• To compare the efficacy of Dato-DXd plus platinum therapy with gemcitabine plus platinum therapy as measured by progression-free survival (PFS) by Blinded Independent Central Review (BICR).
• To compare the efficacy of Dato-DXd plus platinum therapy with gemcitabine plus platinum therapy as measured by overall survival (OS).

Secondary objectives 10

1. Phase 2: To further evaluate the relative efficacy of Dato-DXd 4 mg/kg plus platinum therapy and Dato-DXd 6 mg/kg plus platinum therapy.
2. Phase 2: To evaluate the relative safety and tolerability of Dato-DXd 4 mg/kg plus platinum therapy and Dato-DXd 6 mg/kg plus platinum therapy.
3. Phase 2: To assess the immunogenicity of Dato-DXd.
4. Phase 2: To evaluate the pharmacokinetics (PK) of Dato-DXd and DXd and exposure-response relationships for efficacy and safety.
5. Phase 3: To further evaluate the efficacy of Dato-DXd plus platinum therapy compared with gemcitabine plus platinum therapy.
6. Phase 3: To evaluate the safety and tolerability of Dato-DXd plus platinum therapy compared with gemcitabine plus platinum therapy.
7. Phase 3: To assess the immunogenicity of Dato-DXd.
8. Phase 3: To evaluate the impact of Dato-DXd plus platinum therapy compared with gemcitabine plus platinum therapy on disease-related symptoms as measured by PRO instruments.
9. Phase 3: To evaluate the impact of Dato-DXd plus platinum therapy compared with gemcitabine plus platinum therapy on overall health as measured by PRO instruments.
10. Phase 3: To evaluate the impact of Dato-DXd plus platinum therapy compared with gemcitabine plus platinum therapy on role and physical functioning as measured by PRO instruments.

Conditions and MedDRA coding

Locally Advanced or Metastatic Urothelial Carcinoma

Study design 2 periods

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, European Medicines Agency

Plan to share IPD

Yes

IPD plan description

De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Adult ≥18 years at the time the ICF is signed.
2. Histologically or cytologically confirmed unresectable locally advanced or metastatic urothelial carcinoma of the bladder, renal pelvis, ureter, or urethra.
3. Must provide tumor tissue sample from archival tissue or newly obtained pretreatment biopsy for exploratory biomarker testing.
4. Participant must be considered eligible to receive cisplatin- or carboplatin-containing chemotherapy, in the investigator’s judgment.
5. Must have experienced radiographic progression or relapse during or after 1L of enfortumab vedotin (EV) and pembrolizumab. Participant who discontinued EV and pembrolizumab in 1L due to toxicity are eligible if they have experienced disease progression following discontinuation.
6. Measurable disease on CT/MRI per RECIST version 1.1 as assessed by investigator.
7. ECOG PS of 0 or 1.
8. Has required baseline laboratory data: adequate bone marrow function, adequate renal function, adequate hepatic function, and adequate blood clotting function.

Exclusion criteria 9

1. Has had prior systemic therapy other than the combination of EV and pembrolizumab for la/mUC.
2. Has had treatment with any of the following: History of an allogeneic bone marrow or solid organ transplant, concomitant treatment with any prohibited medications in the protocol, prior TROP2 directed ADC therapy.
3. Uncontrolled or significant cardiovascular disease.
4. Has a 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.
5. Has clinically severe pulmonary compromise as judged by the investigator resulting from intercurrent pulmonary illnesses.
6. Has toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet improved to NCI-CTCAE version 5.0 Grade ≤1 or baseline. Participants may be enrolled with chronic, stable Grade 2 toxicities which the investigator deems related to previous anticancer therapy.
7. History of severe hypersensitivity to either the drug or inactive ingredients of Dato-DXd, platinum (i.e., both carboplatin and cisplatin), or gemcitabine.
8. Has an uncontrolled infection requiring systemic therapy
9. Has clinically significant corneal disease.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Phase 2: ORR, assessed by investigator assessment using RECIST Version 1.1 criteria: defined as the proportion of participants with a BOR of confirmed CR or confirmed PR.
2. Phase 3: PFS, determined by BICR assessment of tumor scans and using RECIST Version 1.1 criteria, defined as the time from randomization to the first documented radiographic disease progression or death due to any cause, whichever occurs first.
3. Phase 3: OS, defined as the time from randomization to death due to any cause.

Secondary endpoints 18

1. Phase 2: DoR, assessed by investigator assessment using RECIST Version 1.1 criteria, 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.
2. Phase 2: PFS, determined by investigator assessment of tumor scans and using RECIST Version 1.1 criteria, 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.
3. Phase 2: OS is defined as the time from randomization to death due to any cause.
4. Phase 2: TTR, assessed by investigator assessment using RECIST Version 1.1 criteria, defined as the time from randomization to the date of the first documentation of objective tumor response (confirmed CR or confirmed PR) in responding participants.
5. Phase 2: DCR, assessed by investigator assessment using RECIST Version 1.1 criteria, is defined as proportion of participants with a BOR of confirmed CR, confirmed PR, or SD.
6. Phase 2: Incidence of TEAEs, SAEs, AESIs, deaths, and changes from baseline in vital signs, standard clinical laboratory parameters, ECG parameters, ECHO/MUGA scan findings, and ophthalmologic findings.
7. Phase 2: ADA incidence.
8. Phase 2: Characterize population PK of Dato-DXd and DXd and the relationship between exposure and efficacy and safety endpoints.
9. Phase 3: PFS, determined by investigator assessment of tumor scans and using RECIST Version 1.1 criteria, 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.
10. Phase 3: ORR, assessed by BICR and investigator assessment using RECIST Version 1.1 criteria, is defined as the proportion of participants with a BOR of confirmed CR or confirmed PR.
11. Phase 3: DoR, assessed by BICR and investigator assessment using RECIST Version 1.1 criteria, 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.
12. Phase 3: TTR, assessed by BICR and investigator assessment using RECIST Version 1.1 criteria, is defined as the time from randomization to the date of the first documentation of objective tumor response (confirmed CR or confirmed PR) in responding participants.
13. Phase 3: DCR, assessed by BICR and investigator assessment using RECIST Version 1.1 criteria, is defined as proportion of participants with a BOR of confirmed CR, confirmed PR, or SD.
14. Phase 3: Incidence of TEAEs, SAEs, AESIs, deaths, and changes from baseline in vital signs, standard clinical laboratory parameters, ECG parameters, ECHO/MUGA scan findings, and ophthalmologic findings.
15. Phase 3: ADA incidence.
16. Phase 3: TTCD, defined as time from the date of randomization to the date of confirmed deterioration, and mean change from baseline in the urinary symptoms subscale of the EORTC-QLQ-BLM30.
17. Phase 3: TTCD, defined as time from the date of randomization to the date of confirmed deterioration, and mean change from baseline in GHS/QoL, as measured by the GHS/QoL scale from EORTC-QLQ-C30.
18. Phase 3: TTCD, defined as time from the date of randomization to the date of confirmed deterioration, and mean change from baseline in physical and role functioning, as measured by the physical functioning and role functioning domains from EORTC-QLQ-C30.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Daiichi Sankyo Inc.

Sponsor organisation

Daiichi Sankyo Inc.

Address

211 Mount Airy Road

City

Basking Ridge

Postcode

07920-2311

Country

United States

Scientific contact point

Organisation

Daiichi Sankyo Inc.

Contact name

Clinical Trial Office

Public contact point

Organisation

Daiichi Sankyo Inc.

Contact name

Clinical Trial Office

Third parties 12

Locations

11 EU/EEA countries · 119 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 128 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

12 submissions — initial application plus substantial / non-substantial modifications