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AzTrials

Bladder CancerPhase 2NCT02625961

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)

A Phase 2 study testing Pembrolizumab, Pembrolizumab/vibostolimab coformulation and Favezelimab/pembrolizumab coformulation in people with Bladder Cancer, run by Merck Sharp & Dohme LLC.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Bladder Cancer
What is being tested?
Pembrolizumab, Pembrolizumab/vibostolimab coformulation and Favezelimab/pembrolizumab coformulation
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
296 participants
Where
No sites listed yet
Study dates
10 Feb 2016to 5 Nov 2025
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

About this study

Official 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

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.

Read the detailed description

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

Conditions
Bladder Cancer
Being tested
Pembrolizumab, Pembrolizumab/vibostolimab coformulation, Favezelimab/pembrolizumab coformulation
Keywords
PD1, PDL1, PD-L1, PD-1
Medical subject headings
Urinary Bladder Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PembrolizumabBiological

    Also called MK-3475, KEYTRUDA

    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

  • Pembrolizumab/vibostolimab coformulationBiological

    Also called MK-7684A

    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

  • Favezelimab/pembrolizumab coformulationBiological

    Also called MK-4280A

    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

Study groups in NCT02625961
Study groupRoleWhat they receive
PembrolizumabExperimentalParticipants 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.
Receives: Biological: Pembrolizumab
Pembrolizumab coformulationExperimentalParticipants 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
Receives: Biological: Pembrolizumab/vibostolimab coformulation; Biological: Favezelimab/pembrolizumab coformulation

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Cohort A: Complete Response (CR) Rate of High-Risk Non-Muscle Invasive Bladder Cancer (NMIBC)

    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.

    Measured: Up to approximately 6 months

  2. Cohort B: 12-month Disease-Free Survival (DFS) Rate of High-Risk NMIBC

    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.

    Measured: Up to approximately 12 months

  3. Cohort A and B: Number of Participants Who Experience an Adverse Event (AE)

    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.

    Measured: Up to approximately 27 months

  4. Cohort A and B: Number of Participants Who Discontinue Study Treatment Due to an AE

    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.

    Measured: Up to approximately 24 months

Secondary outcomes (8)

  1. Cohort A: CR Rate of Any Disease

    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.

    Measured: Up to approximately 6 months

  2. Cohort A: CR Rate of High-Risk NMIBC in Programmed Cell Death 1 (PDL-1) Positive Participants

    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.

    Measured: Up to approximately 6 months

  3. Cohort A: Duration of Response (DOR)

    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.

    Measured: Up to approximately 60 months

  4. Cohort A and B: Progression-Free Survival (PFS)

    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.

    Measured: Up to approximately 60 months

  5. Cohort A and B: Overall Survival (OS)

    OS is defined as the time from first dose to death due to any cause.

    Measured: Up to approximately 60 months

  6. Cohort B: DFS Rate of Any Disease

    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.

    Measured: Up to approximately 60 months

  7. Cohort B: 12-month DFS Rate of Any Disease

    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.

    Measured: Up to approximately 12 months

  8. Cohort B: 12-month DFS Rate of High-Risk NMIBC in PDL-1 Positive Participants

    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.

    Measured: Up to approximately 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Dec 2015 (estimated)
  2. Study start10 Feb 2016
  3. Primary completion5 Nov 2025
  4. Study completion5 Nov 2025

Why it stopped: Business Reasons

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
296 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02625961
Sponsor's protocol ID
3475-057
Other IDs
163236, 2022-502526-41-00, U1111-1284-7618, 2014-004026-17, 2014
Status last verified
Aug 2026
First submitted
7 Dec 2015
Last updated
31 Aug 2026
Results posted
No
Data monitoring committee
Yes
Individual data sharing
Yes: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

Publications

  • 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.

    PubMed 38740030

  • 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.

    PubMed 34051177

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pembrolizumab, Pembrolizumab/vibostolimab coformulation and Favezelimab/pembrolizumab coformulation in people with Bladder Cancer, run by Merck Sharp & Dohme LLC.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 31 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Business Reasons). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Cohort A: Complete Response (CR) Rate of High-Risk Non-Muscle Invasive Bladder Cancer (NMIBC) (time frame: Up to approximately 6 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02625961, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Aug 2026.

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