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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05911295




Registration number
NCT05911295
Ethics application status
Date submitted
9/06/2023
Date registered
22/06/2023
Date last updated
21/08/2024

Titles & IDs
Public title
Disitamab Vedotin With Pembrolizumab vs Chemotherapy in Previously Untreated Urothelial Cancer Expressing HER2
Scientific title
An Open-label, Randomized, Controlled Phase 3 Study of Disitamab Vedotin in Combination With Pembrolizumab Versus Chemotherapy in Subjects With Previously Untreated Locally Advanced or Metastatic Urothelial Carcinoma That Expresses HER2 (IHC 1+ and Greater)
Secondary ID [1] 0 0
KEYNOTE-D74
Secondary ID [2] 0 0
SGNDV-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Urothelial Carcinoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney
Cancer 0 0 0 0
Bladder - transitional cell cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - disitamab vedotin
Treatment: Drugs - pembrolizumab
Treatment: Drugs - gemcitabine
Treatment: Drugs - cisplatin
Treatment: Drugs - carboplatin

Experimental: Disitamab vedotin arm - disitamab vedotin + pembrolizumab

Active comparator: Standard of care arm - gemcitabine + cisplatin OR carboplatin


Treatment: Drugs: disitamab vedotin
Given into the vein (IV; intravenous) every 2 weeks

Treatment: Drugs: pembrolizumab
400mg given by IV every 6 weeks

Treatment: Drugs: gemcitabine
1000 mg/m\^2 given by IV on days 1 and 8 of every 3-week cycle

Treatment: Drugs: cisplatin
70 mg\^2 given by IV on day 1 of every 3-week cycle

Treatment: Drugs: carboplatin
Area under the plasma concentration-time curve (AUC) 4.5 or 5 given by IV on day 1 of every 3-week cycle

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) by blinded independent central review (BICR)
Timepoint [1] 0 0
Approximately 3 years
Primary outcome [2] 0 0
Overall survival (OS)
Timepoint [2] 0 0
Approximately 5 years
Secondary outcome [1] 0 0
Objective response rate (ORR) per RECIST v1.1 by BICR
Timepoint [1] 0 0
Approximately 3 years
Secondary outcome [2] 0 0
ORR per RECIST v1.1 by investigator assessment
Timepoint [2] 0 0
Approximately 3 years
Secondary outcome [3] 0 0
Duration of Response (DOR) per RECIST v1.1 by BICR
Timepoint [3] 0 0
Approximately 3 years
Secondary outcome [4] 0 0
DOR per RECIST v1.1 by investigator assessment
Timepoint [4] 0 0
Approximately 3 years
Secondary outcome [5] 0 0
Control Rate (DCR) per RECIST v1.1 by BICR
Timepoint [5] 0 0
Approximately 3 years
Secondary outcome [6] 0 0
DCR per RECIST v1.1 by investigator assessment
Timepoint [6] 0 0
Approximately 3 years
Secondary outcome [7] 0 0
PFS per RECIST v1.1 by investigator assessment
Timepoint [7] 0 0
Approximately 3 years
Secondary outcome [8] 0 0
Number of participants with adverse events (AEs)
Timepoint [8] 0 0
Through 30 days after the last study treatment; approximately 2 years
Secondary outcome [9] 0 0
Number of participants with laboratory abnormalities
Timepoint [9] 0 0
Through 30 days after the last study treatment; approximately 2 years
Secondary outcome [10] 0 0
Treatment discontinuation rate due to AEs
Timepoint [10] 0 0
Approximately 2 years
Secondary outcome [11] 0 0
Number of electrocardiogram (ECG) abnormalities
Timepoint [11] 0 0
Through 30 days after the last study treatment; approximately 2 years
Secondary outcome [12] 0 0
Change from baseline of left ventricular ejection fraction (LVEF)
Timepoint [12] 0 0
Through 2 years after last study treatment; approximately 4 years
Secondary outcome [13] 0 0
Change from baseline to Week 16 in European Organization for Research and Treatment of Cancer core Quality of Life questionnaire (EORTC QLQ-C30) Global Health Status (GHS)/QoL Score
Timepoint [13] 0 0
Approximately 2 years
Secondary outcome [14] 0 0
Time to Deterioration in EORTC QLQ-C30 GHS/QoL Score
Timepoint [14] 0 0
Approximately 2 years
Secondary outcome [15] 0 0
Time to pain progression
Timepoint [15] 0 0
Approximately 2 years

Eligibility
Key inclusion criteria
* Histopathological confirmation of locally advanced unresectable or metastatic urothelial carcinoma (LA/mUC), including UC originating from the renal pelvis, ureters, bladder, or urethra.
* Measurable disease by investigator assessment per RECIST v1.1.
* Participant must not have received prior systemic therapy for LA/mUC. Exception will be made for neoadjuvant or adjuvant therapy, if disease recurrence/progression occurred more than 12 months after the last dose of therapy.
* Eligible to receive cisplatin- or carboplatin-containing chemotherapy.
* Able to provide archived formalin-fixed paraffin-embedded tumor tissue blocks from a muscle-invasive or metastatic UC lesion or biopsy of metastatic UC prior to treatment initiation. If archival tissue is not available a newly obtained baseline biopsy of an accessible tumor lesion is required within 28 days of cycle 1 day 1.
* HER2 expression of 1+ or greater on immunohistochemistry (IHC).
* Eastern Cooperative Oncology Group (ECOG) performance score of 0, 1, or 2 within 7 days prior to randomization.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Known hypersensitivity to disitamab vedotin, cisplatin, carboplatin, gemcitabine, or pembrolizumab or any of their components.
* History of severe/life threatening immune-related adverse event (irAE) with PD-(L)1 inhibitors are excluded.
* Central nervous system (CNS) and/or leptomeningeal metastasis. Participants with treated CNS metastases are permitted if all of the following are met.

* CNS metastases have been clinically stable for at least 4 weeks and baseline scans show no evidence of new or worsening CNS metastasis.
* Participant is on a stable dose of = 10 mg/day of prednisone or equivalent for at least 2 weeks.
* History of or active autoimmune disease that has required systemic treatment in the past 2 years.
* Prior treatment with an agent directed to another stimulatory or co-inhibitory T cell receptor (including but not limited to CD137 agonists, CAR-T cell therapy, CTLA-4 inhibitors, or OX-40 agonists).
* Prior solid organ or bone marrow transplantation.
* Pleural effusion or ascites with symptoms or requiring symptomatic treatment.
* Estimated life expectancy <12 week
* Prior treatment with an MMAE agent or anti-HER2 therapy

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Othe
Recruitment hospital [1] 0 0
Macquarie University Hospital - Brisbane
Recruitment hospital [2] 0 0
Icon Cancer Care Chermside - Chermside
Recruitment hospital [3] 0 0
Lyell McEwin Hospital - Elizabeth Vale
Recruitment hospital [4] 0 0
Peninsula and South East Oncology - Frankston
Recruitment hospital [5] 0 0
Port Macquarie Base Hospital - Port Macquarie
Recruitment hospital [6] 0 0
Mater Cancer Care Centre - South Brisbane
Recruitment postcode(s) [1] 0 0
2109 - Brisbane
Recruitment postcode(s) [2] 0 0
4032 - Chermside
Recruitment postcode(s) [3] 0 0
5112 - Elizabeth Vale
Recruitment postcode(s) [4] 0 0
3199 - Frankston
Recruitment postcode(s) [5] 0 0
2444 - Port Macquarie
Recruitment postcode(s) [6] 0 0
4101 - South Brisbane
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alaska
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Iowa
Country [6] 0 0
United States of America
State/province [6] 0 0
Maryland
Country [7] 0 0
United States of America
State/province [7] 0 0
Minnesota
Country [8] 0 0
United States of America
State/province [8] 0 0
Mississippi
Country [9] 0 0
United States of America
State/province [9] 0 0
Nebraska
Country [10] 0 0
United States of America
State/province [10] 0 0
New York
Country [11] 0 0
United States of America
State/province [11] 0 0
North Carolina
Country [12] 0 0
United States of America
State/province [12] 0 0
Pennsylvania
Country [13] 0 0
United States of America
State/province [13] 0 0
Tennessee
Country [14] 0 0
United States of America
State/province [14] 0 0
Texas
Country [15] 0 0
United States of America
State/province [15] 0 0
Washington
Country [16] 0 0
United States of America
State/province [16] 0 0
Wisconsin
Country [17] 0 0
Canada
State/province [17] 0 0
Alberta
Country [18] 0 0
Canada
State/province [18] 0 0
British Columbia
Country [19] 0 0
Canada
State/province [19] 0 0
Ontario
Country [20] 0 0
Canada
State/province [20] 0 0
Other
Country [21] 0 0
Singapore
State/province [21] 0 0
Other
Country [22] 0 0
Spain
State/province [22] 0 0
Other
Country [23] 0 0
Taiwan
State/province [23] 0 0
Other

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Seagen Inc.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
RemeGen Co., Ltd.
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/industry
Name [2] 0 0
Merck Sharp & Dohme LLC
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Monitor
Address 0 0
Seagen Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Seagen Trial Information Support
Address 0 0
Country 0 0
Phone 0 0
866-333-7436
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.