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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02625961




Registration number
NCT02625961
Ethics application status
Date submitted
7/12/2015
Date registered
9/12/2015
Date last updated
12/08/2024

Titles & IDs
Public title
Study of Pembrolizumab (MK-3475) and Pembrolizumab With Other Investigational Agents in Participants With High Risk Non-muscle Invasive Bladder Cancer (MK-3475-057/KEYNOTE-057)
Scientific title
A Phase II Clinical Trial to Study the Efficacy and Safety of Pembrolizumab (MK-3475) and Pembrolizumab in Combination With Other Investigational Agents in Subjects With High Risk Non-muscle-Invasive Bladder Cancer (NMIBC) Unresponsive to Bacillus Calmette-Guerin (BCG) Therapy
Secondary ID [1] 0 0
163236
Secondary ID [2] 0 0
3475-057
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Bladder Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bladder - transitional cell cancer
Renal and Urogenital 0 0 0 0
Other renal and urogenital disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Pembrolizumab
Treatment: Other - Pembrolizumab/vibostolimab coformulation
Treatment: Other - Favezelimab/pembrolizumab coformulation

Experimental: Pembrolizumab - Participants with carcinoma-in-situ (CIS) with or without papillary tumors (Cohort A) and participants with papillary tumors only, without CIS (Cohort B) will receive pembrolizumab, 200 mg, intravenously, every 3 weeks (Q3W) for up to 24 months.

Experimental: Pembrolizumab coformulation - Participants with CIS with or without papillary tumors (Cohort C) will receive either pembrolizumab/vibostolimab or favezelimab/pembrolizumab coformulation intravenously Q3W for up to 24 months


Treatment: Other: Pembrolizumab
Participants with CIS with or without papillary tumors (Cohort A) and participants with papillary tumors only, without CIS (Cohort B) receive pembrolizumab 200mg via IV infusion once every 3 weeks for up to 35 administrations

Treatment: Other: Pembrolizumab/vibostolimab coformulation
Participants with CIS with or without papillary tumors (Cohort C) receive pembrolizumab/vibostolimab (coformulation of 200 mg pembrolizumab and 200 mg vibostolimab) via IV infusion once every 3 weeks for up to 35 administrations

Treatment: Other: Favezelimab/pembrolizumab coformulation
Participants with CIS with or without papillary tumors (Cohort C) receive favezelimab/pembrolizumab (coformulation of 800mg favezelimab and 200 mg pembrolizumab) via IV infusion once every 3 weeks for up to 35 administrations
Intervention code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Cohort A: Complete Response (CR) Rate of High-Risk Non-Muscle Invasive Bladder Cancer (NMIBC)
Timepoint [1] 0 0
Up to approximately 6 months
Primary outcome [2] 0 0
Cohort B: 12-month Disease-Free Survival (DFS) Rate of High-Risk NMIBC
Timepoint [2] 0 0
Up to approximately 12 months
Primary outcome [3] 0 0
Cohort C: 12-month CR Rate of High-Risk NMIBC
Timepoint [3] 0 0
Up to approximately 12 months
Primary outcome [4] 0 0
All Cohorts: Number of Participants Who Experience an Adverse Event (AE)
Timepoint [4] 0 0
Up to approximately 27 months
Primary outcome [5] 0 0
All Cohorts: Number of Participants Who Discontinue Study Treatment Due to an AE
Timepoint [5] 0 0
Up to approximately 24 months
Secondary outcome [1] 0 0
Cohort A: CR Rate of Any Disease
Timepoint [1] 0 0
Up to approximately 6 months
Secondary outcome [2] 0 0
Cohort C: CR Rate of High-Risk NMIBC at 3 Months
Timepoint [2] 0 0
Up to approximately 3 months
Secondary outcome [3] 0 0
Cohort C: CR Rate of High-Risk NMIBC at 6 Months
Timepoint [3] 0 0
Up to approximately 6 months
Secondary outcome [4] 0 0
Cohort C: Overall CR Rate of High-Risk NMIBC
Timepoint [4] 0 0
Up to approximately 6 months
Secondary outcome [5] 0 0
Cohort A: CR Rate of High-Risk NMIBC in Programmed Cell Death 1 (PDL-1) Positive Participants
Timepoint [5] 0 0
Up to approximately 6 months
Secondary outcome [6] 0 0
Cohort A and C: Duration of Response (DOR)
Timepoint [6] 0 0
Up to approximately 60 months
Secondary outcome [7] 0 0
All Cohorts: Progression-Free Survival (PFS)
Timepoint [7] 0 0
Up to approximately 60 months
Secondary outcome [8] 0 0
All Cohorts: Overall Survival (OS)
Timepoint [8] 0 0
Up to approximately 60 months
Secondary outcome [9] 0 0
Cohort B: DFS Rate of Any Disease
Timepoint [9] 0 0
Up to approximately 60 months
Secondary outcome [10] 0 0
Cohort B: 12-month DFS Rate of Any Disease
Timepoint [10] 0 0
Up to approximately 12 months
Secondary outcome [11] 0 0
Cohort B: 12-month DFS Rate of High-Risk NMIBC in PDL-1 Positive Participants
Timepoint [11] 0 0
Up to approximately 12 months

Eligibility
Key inclusion criteria
* Histologically-confirmed diagnosis of high risk non-muscle-invasive (T1, high grade Ta and / or carcinoma in situ [CIS]) transitional cell carcinoma of the bladder (mixed histology tumors allowed if transitional cell histology is predominant histology).
* Fully resected disease at study entry (residual CIS acceptable)
* BCG-unresponsive high risk non-muscle-invasive bladder cancer after treatment with adequate BCG therapy
* Ineligible for radical cystectomy or refusal of radical cystectomy
* Available tissue from a newly obtained core biopsy of a tumor lesion not previously irradiated
* Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
* Adequate organ function
* Female participants of childbearing potential have a negative urine or serum pregnancy test and must be willing to use an adequate method of contraception
* Male participants must be willing to use an adequate method of contraception
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

* Centrally assessed muscle-invasive, locally advanced nonresectable, or metastatic urothelial carcinoma (i.e., T2, T3, T4, and / or stage IV)
* Centrally assessed concurrent extra-vesical (i.e., urethra, ureter, or renal pelvis) non-muscle invasive transitional cell carcinoma of the urothelium
* Currently participating or has participated in a study of an investigational agent and received study therapy or received investigational device within 4 weeks prior to the first dose of study treatment
* Received intervening intravesical chemotherapy or immunotherapy from the time of most recent cystoscopy / Transurethral Resection of Bladder Tumor (TURBT) to starting study treatment
* Received prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to starting study treatment or not recovered from adverse events due to a previously administered agent
* Known additional malignancy that is progressing or requires active treatment excepting basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer. A history of prostate cancer that was treated with definitive intent (surgically or through radiation therapy) is acceptable provided that the following criteria are met: Stage T2N0M0 or lower; Gleason score =7 and prostatic-specific antigen (PSA) undetectable for at least 1 year while off androgen deprivation therapy that was either treated with definitive intent or untreated in active surveillance that has been stable for the past year prior to study allocation
* Active autoimmune disease that has required systemic treatment in the past 2 years
* Evidence of interstitial lung disease or active non-infectious pneumonitis
* Active infection requiring systemic therapy
* Pregnant or breastfeeding, or expecting to conceive within the projected duration of the trial through 120 days after the last dose of study treatment
* Prior therapy with an anti-programmed cell death 1 (PD-1), anti-PD-ligand 2 (L2) agent, or with an agent directed to another co-inhibitory T-cell receptor
* Known human immunodeficiency virus (HIV)
* Known active Hepatitis B or C infection
* Received a live virus vaccine within 30 days of planned start of study treatment
* Has had an allogeneic 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 2
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
10/02/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/08/2030
Actual
Sample size
Target
320
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
MSD Australia - North Ryde
Recruitment postcode(s) [1] 0 0
- North Ryde
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
Illinois
Country [3] 0 0
United States of America
State/province [3] 0 0
Indiana
Country [4] 0 0
United States of America
State/province [4] 0 0
Kansas
Country [5] 0 0
United States of America
State/province [5] 0 0
Minnesota
Country [6] 0 0
United States of America
State/province [6] 0 0
New Jersey
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
Ohio
Country [9] 0 0
United States of America
State/province [9] 0 0
Pennsylvania
Country [10] 0 0
United States of America
State/province [10] 0 0
South Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Texas
Country [12] 0 0
Brazil
State/province [12] 0 0
Sao Paulo
Country [13] 0 0
Canada
State/province [13] 0 0
Quebec
Country [14] 0 0
Finland
State/province [14] 0 0
Espoo
Country [15] 0 0
France
State/province [15] 0 0
Paris
Country [16] 0 0
Italy
State/province [16] 0 0
Rome
Country [17] 0 0
Netherlands
State/province [17] 0 0
Haarlem
Country [18] 0 0
Puerto Rico
State/province [18] 0 0
Ponce
Country [19] 0 0
Puerto Rico
State/province [19] 0 0
Rio Piedras
Country [20] 0 0
Singapore
State/province [20] 0 0
Singapore
Country [21] 0 0
Spain
State/province [21] 0 0
Madrid
Country [22] 0 0
Turkey
State/province [22] 0 0
Istanbul

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

Ethics approval
Ethics application status

Summary
Brief summary
In this study, participants with high risk non-muscle-invasive bladder cancer (NMIBC) unresponsive to Bacillus Calmette Guerin (BCG) therapy and who are considered ineligible for or have refused to undergo radical cystectomy, will receive pembrolizumab therapy or pembrolizumab in combination with other investigational agents. The primary study hypothesis is that treatment with pembrolizumab will result in a clinically meaningful response.
Trial website
https://clinicaltrials.gov/study/NCT02625961
Trial related presentations / publications
Balar AV, Kamat AM, Kulkarni GS, Uchio EM, Boormans JL, Roumiguie M, Krieger LEM, Singer EA, Bajorin DF, Grivas P, Seo HK, Nishiyama H, Konety BR, Li H, Nam K, Kapadia E, Frenkl T, de Wit R. Pembrolizumab monotherapy for the treatment of high-risk non-muscle-invasive bladder cancer unresponsive to BCG (KEYNOTE-057): an open-label, single-arm, multicentre, phase 2 study. Lancet Oncol. 2021 Jul;22(7):919-930. doi: 10.1016/S1470-2045(21)00147-9. Epub 2021 May 26. Erratum In: Lancet Oncol. 2021 Aug;22(8):e347. doi: 10.1016/S1470-2045(21)00414-9.
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
Toll Free Number
Address 0 0
Country 0 0
Phone 0 0
1-888-577-8839
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT02625961