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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT02625961
Registration number
NCT02625961
Ethics application status
Date submitted
7/12/2015
Date registered
9/12/2015
Date last updated
7/03/2024
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)
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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
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Secondary ID [1]
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163236
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Secondary ID [2]
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3475-057
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Bladder Cancer
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Condition category
Condition code
Cancer
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Bladder - transitional cell cancer
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Renal and Urogenital
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Other renal and urogenital disorders
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Other interventions - Pembrolizumab
Other interventions - Pembrolizumab/vibostolimab coformulation
Other interventions - 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
Other interventions: 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
Other interventions: 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
Other interventions: 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
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Intervention code [1]
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Other interventions
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Cohort A: Complete Response (CR) Rate of High-Risk Non-Muscle Invasive Bladder Cancer (NMIBC)
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Assessment method [1]
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The CR rate of high-risk NMIBC is defined as the proportion of participants in the analysis population whose tumors are in response to treatment and who are then free of high-risk NMIBC or worse per central pathology and radiology review.
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Timepoint [1]
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Up to approximately 6 months
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Primary outcome [2]
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Cohort B: 12-month Disease-Free Survival (DFS) Rate of High-Risk NMIBC
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Assessment method [2]
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DFS of high-risk NMIBC is defined as the time from the first dose to the first occurrence of high-risk NMIBC or worse per central pathology and radiology review. The 12-month DFS rate is the percentage of participants remaining free from high-risk NMIBC or worse at 12 months.
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Timepoint [2]
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Up to approximately 12 months
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Primary outcome [3]
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Cohort C: 12-month CR Rate of High-Risk NMIBC
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Assessment method [3]
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The 12-month CR rate of high-risk NMIBC is defined as the proportion of participants in the analysis population whose tumors are in response to treatment and who are then free of high-risk NMIBC or worse per central pathology and radiology review at 12 months.
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Timepoint [3]
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Up to approximately 12 months
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Primary outcome [4]
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All Cohorts: Number of Participants Who Experience an Adverse Event (AE)
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Assessment method [4]
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An AE is defined as any untoward medical occurrence in a participant or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
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Timepoint [4]
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Up to approximately 27 months
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Primary outcome [5]
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All Cohorts: Number of Participants Who Discontinue Study Treatment Due to an AE
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Assessment method [5]
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An AE is defined as any untoward medical occurrence in a participant or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
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Timepoint [5]
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Up to approximately 24 months
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Secondary outcome [1]
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Cohort A: CR Rate of Any Disease
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Assessment method [1]
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The CR rate of any disease is defined as the proportion of participants in the analysis population whose tumors are in response to treatment and who are then free of any disease or worse per central pathology and radiology review.
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Timepoint [1]
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Up to approximately 6 months
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Secondary outcome [2]
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Cohort C: CR Rate of High-Risk NMIBC at 3 Months
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Assessment method [2]
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The CR rate of high-risk NMIBC at 3 months is defined as the proportion of participants in the analysis population whose tumors are in response to treatment and who are then free of high-risk NMIBC or worse per central pathology and radiology review at 3 months.
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Timepoint [2]
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Up to approximately 3 months
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Secondary outcome [3]
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Cohort C: CR Rate of High-Risk NMIBC at 6 Months
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Assessment method [3]
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The CR rate of high-risk NMIBC at 6 months is defined as the proportion of participants in the analysis population whose tumors are in response to treatment and who are then free of high-risk NMIBC or worse per central pathology and radiology review at 6 months.
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Timepoint [3]
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Up to approximately 6 months
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Secondary outcome [4]
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Cohort C: Overall CR Rate of High-Risk NMIBC
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Assessment method [4]
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The overall CR rate of high-risk NMIBC is defined as the proportion of participants in the analysis population whose tumors are in response to treatment and who are then free of high-risk NMIBC or worse per central pathology and radiology review at first evaluable efficacy assessment.
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Timepoint [4]
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Up to approximately 6 months
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Secondary outcome [5]
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Cohort A: CR Rate of High-Risk NMIBC in Programmed Cell Death 1 (PDL-1) Positive Participants
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Assessment method [5]
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The CR of high-risk NMIBC is defined as the proportion of PDL-1 positive participants in the analysis population whose tumors are in response to treatment and who are then free of high-risk NMIBC or worse per central pathology and radiology review.
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Timepoint [5]
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Up to approximately 6 months
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Secondary outcome [6]
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Cohort A and C: Duration of Response (DOR)
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Assessment method [6]
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The DOR is defined as the time from the first documented evidence of CR until the recurrence of disease or worse per clinical pathology and radiology review.
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Timepoint [6]
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Up to approximately 60 months
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Secondary outcome [7]
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All Cohorts: Progression-Free Survival (PFS)
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Assessment method [7]
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PFS is defined as the time from the first dose to progression to worsening of grade or stage or death or to muscle invasive or metastatic disease or death per central urology, pathology, and radiology review.
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Timepoint [7]
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Up to approximately 60 months
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Secondary outcome [8]
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All Cohorts: Overall Survival (OS)
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Assessment method [8]
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OS is defined as the time from first dose to death due to any cause.
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Timepoint [8]
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Up to approximately 60 months
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Secondary outcome [9]
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Cohort B: DFS Rate of Any Disease
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Assessment method [9]
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DFS of any disease is defined as the time from the first dose to the first occurrence of any disease or worse per central pathology and radiology review. The DFS rate is the percentage of participants remaining free of any disease or worse.
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Timepoint [9]
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Up to approximately 60 months
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Secondary outcome [10]
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Cohort B: 12-month DFS Rate of Any Disease
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Assessment method [10]
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DFS of any disease is defined as the time from the first dose to the first occurrence of any disease or worse per central pathology and radiology review. The 12-month DFS rate of any disease is the percentage of participants remaining free of any disease or worse at 12 months.
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Timepoint [10]
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Up to approximately 12 months
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Secondary outcome [11]
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Cohort B: 12-month DFS Rate of High-Risk NMIBC in PDL-1 Positive Participants
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Assessment method [11]
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DFS of high-risk NMIBC is defined as the time from the first dose to the first occurrence of high-risk NMIBC or worse per central pathology and radiology review. The 12-month DFS rate is the percentage of participants remaining free from high-risk NMIBC or worse at 12 months. The 12-month DFS rate of high-risk NMIBC in PDL-1 positive participants will be reported.
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Timepoint [11]
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Up to approximately 12 months
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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
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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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
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 2
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Recruiting
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
10/02/2016
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
31/08/2030
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Actual
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Sample size
Target
320
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Accrual to date
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Final
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Recruitment in Australia
Recruitment state(s)
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Recruitment hospital [1]
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MSD Australia - North Ryde
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Recruitment postcode(s) [1]
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- North Ryde
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Recruitment outside Australia
Country [1]
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United States of America
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State/province [1]
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California
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Country [2]
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United States of America
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State/province [2]
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Indiana
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Country [3]
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United States of America
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State/province [3]
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Kansas
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Country [4]
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United States of America
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State/province [4]
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Minnesota
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Country [5]
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United States of America
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State/province [5]
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New Jersey
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Country [6]
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United States of America
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State/province [6]
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New York
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Country [7]
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United States of America
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State/province [7]
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Ohio
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Country [8]
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United States of America
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State/province [8]
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Pennsylvania
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Country [9]
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United States of America
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State/province [9]
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South Carolina
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Country [10]
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United States of America
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State/province [10]
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Texas
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Country [11]
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Brazil
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State/province [11]
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Sao Paulo
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Country [12]
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Canada
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State/province [12]
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Quebec
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Country [13]
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Finland
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State/province [13]
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Espoo
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Country [14]
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France
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State/province [14]
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Paris
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Country [15]
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Italy
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State/province [15]
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Rome
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Country [16]
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Netherlands
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State/province [16]
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Haarlem
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Country [17]
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Puerto Rico
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State/province [17]
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Ponce
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Country [18]
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Puerto Rico
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State/province [18]
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Rio Piedras
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Country [19]
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Singapore
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State/province [19]
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Singapore
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Country [20]
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Spain
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State/province [20]
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Madrid
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Country [21]
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Turkey
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State/province [21]
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Istanbul
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
Merck Sharp & Dohme LLC
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Address
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Country
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Ethics approval
Ethics application status
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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.
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Trial website
https://clinicaltrials.gov/ct2/show/NCT02625961
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Medical Director
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Address
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Merck Sharp & Dohme LLC
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Country
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Phone
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Fax
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Email
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Contact person for public queries
Name
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Toll Free Number
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Address
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Country
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Phone
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1-888-577-8839
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Fax
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Email
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT02625961
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