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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
13/11/2024

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
22/09/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/04/2029
Actual
Sample size
Target
700
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 hospital [7] 0 0
Royal North Shore Hospital - St Leonards
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 postcode(s) [7] 0 0
2065 - St Leonards
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
Nevada
Country [11] 0 0
United States of America
State/province [11] 0 0
New York
Country [12] 0 0
United States of America
State/province [12] 0 0
North Carolina
Country [13] 0 0
United States of America
State/province [13] 0 0
Pennsylvania
Country [14] 0 0
United States of America
State/province [14] 0 0
Tennessee
Country [15] 0 0
United States of America
State/province [15] 0 0
Texas
Country [16] 0 0
United States of America
State/province [16] 0 0
Virginia
Country [17] 0 0
United States of America
State/province [17] 0 0
Washington
Country [18] 0 0
United States of America
State/province [18] 0 0
Wisconsin
Country [19] 0 0
Argentina
State/province [19] 0 0
Other
Country [20] 0 0
Argentina
State/province [20] 0 0
Caba
Country [21] 0 0
Brazil
State/province [21] 0 0
Other
Country [22] 0 0
Canada
State/province [22] 0 0
Alberta
Country [23] 0 0
Canada
State/province [23] 0 0
British Columbia
Country [24] 0 0
Canada
State/province [24] 0 0
Ontario
Country [25] 0 0
Canada
State/province [25] 0 0
Other
Country [26] 0 0
Chile
State/province [26] 0 0
Other
Country [27] 0 0
France
State/province [27] 0 0
Other
Country [28] 0 0
Israel
State/province [28] 0 0
Other
Country [29] 0 0
Italy
State/province [29] 0 0
Other
Country [30] 0 0
Korea, Republic of
State/province [30] 0 0
Other
Country [31] 0 0
Peru
State/province [31] 0 0
Other
Country [32] 0 0
Peru
State/province [32] 0 0
Lima
Country [33] 0 0
Singapore
State/province [33] 0 0
Other
Country [34] 0 0
Spain
State/province [34] 0 0
Other
Country [35] 0 0
Spain
State/province [35] 0 0
Valencia
Country [36] 0 0
Taiwan
State/province [36] 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
clinicaltrials@seagen.com
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.

Results not provided in https://clinicaltrials.gov/study/NCT05911295