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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05845814




Registration number
NCT05845814
Ethics application status
Date submitted
26/04/2023
Date registered
6/05/2023

Titles & IDs
Public title
A Study of Efficacy and Safety of Pembrolizumab Plus Enfortumab Vedotin (EV) +/- Investigational Agents in First-Line Metastatic Urothelial Carcinoma (mUC) (MK-3475-04B/KEYMAKER-U04)
Scientific title
A Phase 1/2 Randomized, Umbrella Study to Evaluate the Safety and Efficacy of Pembrolizumab Plus Enfortumab Vedotin (EV) in Combination With Investigational Agents Versus Pembrolizumab Plus EV, as First-Line Treatment for Participants With Advanced Urothelial Carcinoma (KEYMAKER-U04): Substudy 04B
Secondary ID [1] 0 0
MK-3475-04B
Secondary ID [2] 0 0
3475-04B
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Urothelial Carcinoma 0 0
Urothelial Neoplasms 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: Other - Coformulated favezelimab/pembrolizumab
Treatment: Other - Coformulated vibostolimab/pembrolizumab
Other interventions - EV
Treatment: Other - Pembrolizumab

Experimental: Arm A: Coformulated favezelimab/pembrolizumab plus EV - Participants will receive coformulated favezelimab/pembrolizumab (800 mg/200 mg) as an intravenous (IV) infusion on Day 1 of every 3-week cycle for up to \~2 years (35 cycles) and EV at 1.25 mg/kg, administered as an IV infusion on Days 1 and 8 of every 3-week cycle until disease progression, intolerable toxicity, or investigator decision.

Experimental: Arm B: Coformulated vibostolimab/pembrolizumab plus EV - Participants will receive coformulated vibostolimab/pembrolizumab (200 mg/200 mg) as an IV infusion on Day 1 of every 3-week cycle, for up to \~2 years (35 cycles) and EV at 1.25 mg/kg, administered as an IV infusion on Days 1 and 8 of every 3-week cycle until disease progression, intolerable toxicity, or investigator decision.

Active comparator: Arm C: Pembrolizumab plus EV - Participants will receive 200 mg pembrolizumab as an IV infusion on Day 1 of every 3-week cycle for up to \~2 years (35 cycles) and EV at 1.25 mg/kg, administered as an IV infusion on Days 1 and 8 of every 3-week cycle, until disease progression, intolerable toxicity, or investigator decision.


Treatment: Other: Coformulated favezelimab/pembrolizumab
Coformulated favezelimab/pembrolizumab (800 mg/200 mg) IV infusion

Treatment: Other: Coformulated vibostolimab/pembrolizumab
Coformulated vibostolimab/pembrolizumab (200 mg/200 mg) IV infusion

Other interventions: EV
1.25 mg/kg IV infusion

Treatment: Other: Pembrolizumab
200 mg IV infusion

Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Part 1: Objective Response Rate (ORR)
Timepoint [1] 0 0
Up to ~4 years
Primary outcome [2] 0 0
Part 1: Percentage of Participants experiencing an Adverse Event (AE)
Timepoint [2] 0 0
Up to ~4 years
Primary outcome [3] 0 0
Part 1: Percentage of Participants who Discontinue study interventions due to an AE
Timepoint [3] 0 0
Up to ~4 years
Primary outcome [4] 0 0
Part 1: Percentage of Participants with Dose-limiting toxicities (DLT)
Timepoint [4] 0 0
Up to 21 days
Primary outcome [5] 0 0
Part 2: Progression Free Survival (PFS)
Timepoint [5] 0 0
Up to ~4 years
Secondary outcome [1] 0 0
Part 1: PFS
Timepoint [1] 0 0
Up to ~4 years
Secondary outcome [2] 0 0
Part 1: Duration of Response (DOR)
Timepoint [2] 0 0
Up to ~4 years
Secondary outcome [3] 0 0
Part 2: Overall Survival (OS)
Timepoint [3] 0 0
Up to ~4 years
Secondary outcome [4] 0 0
Part 2: ORR
Timepoint [4] 0 0
Up to ~4 years
Secondary outcome [5] 0 0
Part 2: DOR
Timepoint [5] 0 0
Up to ~4 years
Secondary outcome [6] 0 0
Part 2: Percentage of Participants experiencing an Adverse Event (AE)
Timepoint [6] 0 0
Up to ~4 years
Secondary outcome [7] 0 0
Part 2: Percentage of Participants who Discontinue study interventions due to an AE
Timepoint [7] 0 0
Up to ~4 years
Secondary outcome [8] 0 0
Part 2: Percentage of Participants with Dose-limiting toxicities (DLT)
Timepoint [8] 0 0
Up to 21 days
Secondary outcome [9] 0 0
Part 1: Mean Change from baseline in the global health status/quality of life of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLC-C30) (Items 29 and 30)
Timepoint [9] 0 0
Baseline and up to ~4 years
Secondary outcome [10] 0 0
Part 1: Mean Change from baseline in the physical functioning scale of the EORTC QLQ-C30
Timepoint [10] 0 0
Baseline and up to ~4 years
Secondary outcome [11] 0 0
Part 1: Mean Change from Baseline in the European Quality of Life 5 Dimensions, 5-level Questionnaire (EQ-5D-5L) visual analog score (VAS)
Timepoint [11] 0 0
Baseline and up to ~4 years
Secondary outcome [12] 0 0
Part 2: Mean Change from baseline in the global health status/quality of life of the EORTC QLC-C30 (Items 29 and 30)
Timepoint [12] 0 0
Baseline and up to ~4 years
Secondary outcome [13] 0 0
Part 2: Mean Change from baseline in the physical functioning scale of the EORTC QLQ-C30
Timepoint [13] 0 0
Baseline and up to ~4 years
Secondary outcome [14] 0 0
Part 2: Mean Change from Baseline in the EQ-5D-5L visual analog score (VAS)
Timepoint [14] 0 0
Baseline and up to ~4 years
Secondary outcome [15] 0 0
Part 1: Time-to-Deterioration (TTD) for the global health status/quality of life of the EORTC QLQ-C30 (Items 29 and 30)
Timepoint [15] 0 0
Up to ~4 years
Secondary outcome [16] 0 0
Part 1: TTD for the physical functioning scale of the EORTC QLQ-C30
Timepoint [16] 0 0
Up to ~4 years
Secondary outcome [17] 0 0
Part 1: TTD for the EQ-5D-5L VAS
Timepoint [17] 0 0
Up to ~4 years
Secondary outcome [18] 0 0
Part 2: TTD for the global health status/quality of life of the EORTC QLQ-C30 (Items 29 and 30)
Timepoint [18] 0 0
Up to ~4 years
Secondary outcome [19] 0 0
Part 2: TTD for the physical functioning scale of the EORTC QLQ-C30
Timepoint [19] 0 0
Up to ~4 years
Secondary outcome [20] 0 0
Part 2: TTD for the EQ-5D-5L VAS
Timepoint [20] 0 0
Up to ~4 years

Eligibility
Key inclusion criteria
* Must have histologically documented, locally advanced/metastatic urothelial carcinoma (la/mUC).

* Participants with mixed histology are eligible provided the urothelial component is =50% (and <10% plasmacytoid component)
* Participants whose tumors contain any neuroendocrine component are not eligible (variant histology to be confirmed locally)
* Must not have received prior systemic therapy for la/mUC. The following therapies in earlier disease setting (eg, muscle-invasive urothelial carcinoma (MIUC)) are permitted:

* Participants that received neoadjuvant or adjuvant chemotherapy are permitted.
* Participants who received anti- programmed cell death 1 protein (PD-1) or programmed cell death ligand 1 (PD-L1) therapy for an earlier disease stage (eg, NMIBC, MIUC) with progression/recurrence >12 months from completion of therapy are permitted.
* Must provide an archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion demonstrating UC, not previously irradiated, and adequate for biomarker evaluation. A newly obtained biopsy is strongly preferred, but not required if archival tissue is evaluable.
* Any AEs due to previous anticancer therapies must have recovered to =Grade 1 or baseline. Endocrine-related AEs adequately treated with hormone replacement or with <Grade 2 neuropathy are eligible.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Has a known additional malignancy, except if the participant has undergone potentially curative therapy with no evidence of that disease recurrence for at least 3 years since initiation of that therapy.
* Central nervous system (CNS) metastases are permitted on-study if all of the following are true: a) CNS metastases have been clinically stable for at least 4 weeks prior to screening and baseline scans show no evidence of new or enlarged metastasis; b) the participant is on a stable dose of =10 mg/day of prednisone or equivalent for at least 2 weeks (if requiring steroid treatment); c) participant does not have leptomeningeal disease.
* Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study intervention.
* Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration.
* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study intervention. Inhaled or topical steroids are permitted in the absence of active autoimmune disease. Physiologic replacement doses of corticosteroids are permitted for participants with adrenal insufficiency.
* Has active keratitis or corneal ulcerations. Superficial punctate keratitis is allowed if the disorder is being adequately treated in the opinion of the investigator.
* Has an active autoimmune disease that has required systemic treatment in past 2 years except replacement therapy.
* Has a history of uncontrolled diabetes.
* Has a history of (noninfectious) pneumonitis that required steroids or has current pneumonitis
* Has an active infection (viral, bacterial, or fungal) requiring systemic therapy.
* Has a known history of human immunodeficiency virus (HIV) infection.
* Has hepatitis B or hepatitis C virus infection.
* Has had major surgery within 4 weeks prior to first dose of study intervention.
* Has had an allogenic tissue/solid organ transplant

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 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not 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)
QLD,VIC
Recruitment hospital [1] 0 0
Royal Brisbane and Women's Hospital-Medical Oncology Clinical Trials Unit, Cancer Care Services ( Si - Brisbane
Recruitment hospital [2] 0 0
Austin Health-Cancer Clinical Trials Centre ( Site 3950) - Heidelberg
Recruitment postcode(s) [1] 0 0
4029 - Brisbane
Recruitment postcode(s) [2] 0 0
3084 - Heidelberg
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Indiana
Country [5] 0 0
United States of America
State/province [5] 0 0
Missouri
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
Ohio
Country [8] 0 0
United States of America
State/province [8] 0 0
Pennsylvania
Country [9] 0 0
United States of America
State/province [9] 0 0
Utah
Country [10] 0 0
Canada
State/province [10] 0 0
Ontario
Country [11] 0 0
Chile
State/province [11] 0 0
Region M. De Santiago
Country [12] 0 0
Chile
State/province [12] 0 0
Valparaiso
Country [13] 0 0
Chile
State/province [13] 0 0
Antofagasta
Country [14] 0 0
France
State/province [14] 0 0
Aquitaine
Country [15] 0 0
France
State/province [15] 0 0
Cote-d Or
Country [16] 0 0
France
State/province [16] 0 0
Haute-Garonne
Country [17] 0 0
France
State/province [17] 0 0
Ile-de-France
Country [18] 0 0
France
State/province [18] 0 0
Rhone
Country [19] 0 0
Israel
State/province [19] 0 0
Haifa
Country [20] 0 0
Israel
State/province [20] 0 0
Petah Tikva
Country [21] 0 0
Israel
State/province [21] 0 0
Ramat Gan
Country [22] 0 0
Italy
State/province [22] 0 0
Lombardia
Country [23] 0 0
Italy
State/province [23] 0 0
Napoli
Country [24] 0 0
Korea, Republic of
State/province [24] 0 0
Seoul
Country [25] 0 0
Netherlands
State/province [25] 0 0
Limburg
Country [26] 0 0
Netherlands
State/province [26] 0 0
Noord-Holland
Country [27] 0 0
Netherlands
State/province [27] 0 0
Zuid-Holland
Country [28] 0 0
Spain
State/province [28] 0 0
Barcelona
Country [29] 0 0
Spain
State/province [29] 0 0
Madrid
Country [30] 0 0
Taiwan
State/province [30] 0 0
Kaohsiung
Country [31] 0 0
Taiwan
State/province [31] 0 0
Tainan
Country [32] 0 0
Taiwan
State/province [32] 0 0
Taipei
Country [33] 0 0
United Kingdom
State/province [33] 0 0
London, City Of

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Merck Sharp & Dohme LLC
Address
Country

Ethics approval
Ethics application status

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

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: http://engagezone.msd.com/ds_documentation.php


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.