NCT02625961 · CITED IN SOURCE DOCUMENTS

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)

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE2
Status at capture: TERMINATED
Registry last update: 2026-08-31

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

No posted result sections were captured. Registered plans do not establish that a treatment works.

Who could take part

eligibility Criteria: 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 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
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
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.
intervention Names
Biological: Pembrolizumab
label
Pembrolizumab
type
EXPERIMENTAL
description
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
intervention Names
Biological: Pembrolizumab/vibostolimab coformulation
Biological: Favezelimab/pembrolizumab coformulation
label
Pembrolizumab coformulation
type
EXPERIMENTAL

interventions

arm Group Labels
Pembrolizumab
description
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
name
Pembrolizumab
other Names
MK-3475
KEYTRUDA
type
BIOLOGICAL
arm Group Labels
Pembrolizumab coformulation
description
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
name
Pembrolizumab/vibostolimab coformulation
other Names
MK-7684A
type
BIOLOGICAL
arm Group Labels
Pembrolizumab coformulation
description
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
name
Favezelimab/pembrolizumab coformulation
other Names
MK-4280A
type
BIOLOGICAL

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 296
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
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.
measure
Cohort A: Complete Response (CR) Rate of High-Risk Non-Muscle Invasive Bladder Cancer (NMIBC)
time Frame
Up to approximately 6 months
description
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.
measure
Cohort B: 12-month Disease-Free Survival (DFS) Rate of High-Risk NMIBC
time Frame
Up to approximately 12 months
description
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.
measure
Cohort A and B: Number of Participants Who Experience an Adverse Event (AE)
time Frame
Up to approximately 27 months
description
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.
measure
Cohort A and B: Number of Participants Who Discontinue Study Treatment Due to an AE
time Frame
Up to approximately 24 months

secondary Outcomes

description
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.
measure
Cohort A: CR Rate of Any Disease
time Frame
Up to approximately 6 months
description
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.
measure
Cohort A: CR Rate of High-Risk NMIBC in Programmed Cell Death 1 (PDL-1) Positive Participants
time Frame
Up to approximately 6 months
description
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.
measure
Cohort A: Duration of Response (DOR)
time Frame
Up to approximately 60 months
description
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.
measure
Cohort A and B: Progression-Free Survival (PFS)
time Frame
Up to approximately 60 months
description
OS is defined as the time from first dose to death due to any cause.
measure
Cohort A and B: Overall Survival (OS)
time Frame
Up to approximately 60 months
description
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.
measure
Cohort B: DFS Rate of Any Disease
time Frame
Up to approximately 60 months
description
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.
measure
Cohort B: 12-month DFS Rate of Any Disease
time Frame
Up to approximately 12 months
description
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.
measure
Cohort B: 12-month DFS Rate of High-Risk NMIBC in PDL-1 Positive Participants
time Frame
Up to approximately 12 months

Full study description

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.
detailed Description: Effective as of Amendment 12, Cohort C was made exploratory, and all Cohort C outcome measures were made exploratory.

Source references

references

citation
Necchi A, Roumiguie M, Kamat AM, Shore ND, Boormans JL, Esen AA, Lebret T, Kandori S, Bajorin DF, Krieger LEM, Niglio SA, Uchio EM, Seo HK, de Wit R, Singer EA, Grivas P, Nishiyama H, Li H, Baranwal P, Van den Sigtenhorst-Fijlstra M, Kapadia E, Kulkarni GS. Pembrolizumab monotherapy for high-risk non-muscle-invasive bladder cancer without carcinoma in situ and unresponsive to BCG (KEYNOTE-057): a single-arm, multicentre, phase 2 trial. Lancet Oncol. 2024 Jun;25(6):720-730. doi: 10.1016/S1470-2045(24)00178-5. Epub 2024 May 10.
pmid
38740030
type
DERIVED
citation
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.
pmid
34051177
type
DERIVED