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Bladder CancerPhase 2NCT03504163

Pembrolizumab (MK-3475) and Bacillus Calmette-Guérin (BCG) as First-Line Treatment for High-Risk T1 Non-Muscle-Invasive Bladder Cancer (NMIBC) and High-Grade Non-Muscle-Invasive Upper Tract Urothelial Carcinoma (NMI-UTUC)]

A Phase 2 study testing Pembrolizumab (MK-3475) and Bacillus Calmette-Guérin (BCG) in people with Bladder Cancer, run by Memorial Sloan Kettering Cancer Center at 7 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

The purpose of this study is to find out the effectiveness of pembrolizumab in combination with BCG as a first line therapy for participants with high grade T1 bladder cancer who are at "high risk" for BCG alone to be ineffective and are seeking an alternative treatment option to radical cystectomy. 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 (MK-3475) and Bacillus Calmette-Guérin (BCG)
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
45 participants
Where
7 sitesUnited States
Study dates
27 Jun 2018to Apr 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

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

  • Be willing and able to provide written informed consent/assent for the trial.
  • Histologically confirmed urothelial cancer by TURBT performed at MSK for patients in the T1 bladder cancer cohort or by high-grade cytology/biopsy by ureteroscopy performed at MSK for patients in the NMI-UTUC cohort.
  • TURBT within 8 weeks of protocol entry with complete resection of all papillary lesions for patients in the T1 bladder cancer cohort and ureteroscopy within 8 weeks of protocol entry with complete ablation of all papillary lesions with ureteroscopy or through antegrade percutaneous access for patients in the NMI-UTUC cohort..
  • Patients in the T1 bladder cancer cohort must have high risk, BCG-naïve non-muscle-invasive urothelial cancer defined as having one of the following disease states:
  • T1 on restaging biopsy, plus CIS
  • Multiple (≥ 1) T1 recurrences, plus CIS
Show all 32Show fewer
  • Multifocal T1 plus CIS
  • T1b (extensive/deep invasion into lamina propria) plus CIS
  • Lymphovascular invasion plus CIS
  • T1 with variant histology: including micropapillary, nested variant, poorly differentiated, squamous, and glandular differentiation (the presence of variant histology will be based on MSKCC review), plus CIS.
  • T1 with urothelial carcinoma of prostatic urethra (Ta, Tis, or T1 within prostatic urethra), plus CIS
  • Large (≥3 cm) T1 tumor, plus CIS
  • Patients in the NMI-UTUC cohort must have high risk, BCG naïve NMI-UTUC, defined by having one of the following disease states:
  • Histologic confirmed ureteroscopic biopsy with clinical stage Tis (also known as CIS), Ta, or T1 disease in the renal pelvis. Concomitant ureteral disease will be allowed if completely treated endoscopically.
  • Clinical stage Tis confirmed by a positive high-grade selective cytology, coupled with ureteroscopic evaluation, confirming only flat eryethematous lesions and the absence of papillary tumors.
  • Must not have received prior treatment with percutaneous BCG to the involved renal unit, but prior intravesical BCG for bladder cancer is acceptable.
  • Patients must have cross sectional imaging (CT or MRI urogram) within 3 months of protocol entry demonstrating no evidence of metastasis or radiographic evidence of muscle invasive disease.
  • Patient refusal of cystectomy and bilateral pelvic lymphadenectomy for the T1 bladder cancer cohort, or refusal of radical nephroureterectomy for NMI-UTUC cohort.
  • No prior intravesical BCG therapy for patients in the T1 bladder cancer cohort.
  • No prior radiation therapy for bladder cancer for patients in the T1 bladder cancer cohort. Prior radiation therapy for prostate cancer is allowed.
  • ECOG performance status of 0 or 1.
  • Age ≥ 18 years.
  • Female subjects of childbearing potential must be willing to use 2 methods of birth control, be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of the study medication (reference section 9.5.2). Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for >1 year.
  • Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.
  • Patients must not have other invasive malignancies within the past 5 years (with the exception of non-melanoma skin cancers, localized prostate cancer, and CIS of the cervix).
  • Required initial laboratory values:
  • Absolute neutrophil count ≥ 1.5 x 10^9/L
  • Platelets ≥ 100 x 10^9/L
  • Hemoglobin ≥ 9 g/dL
  • Bilirubin ≤ 1.5 times the upper limit of normal (x ULN)
  • Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 x ULN
  • Calculated creatinine clearance ≥ 30 using the CKD-Epi formula

Who cannot join

  • Current or History of muscle invasive bladder cancer or prostatic stromal invasion.
  • Unstable angina
  • New York Heart Association (NYHA) Grade II or greater congestive heart failure
  • History of myocardial infarction within 6 months
  • History of stroke within 6 months
  • Evidence of bleeding diathesis or coagulopathy
Show all 22Show fewer
  • Presence of any systemic metastases (i.e, nodal, visceral, or central nervous system)
  • Major surgical procedure (other than TURBT or ureteroscopy) within 28 days prior to the study
  • Pregnant (positive pregnancy test) or lactating
  • Serious, non-healing wound, ulcer, or bone fracture
  • Inability to comply with study and/or follow-up procedures
  • Prior therapy with an anti-PD-1 agent, anti-PD-L1 agent, or other inhibitory or stimulatory agent oriented towards a T-cell receptor
  • Active infection requiring systemic therapy
  • Known history of human immunodeficiency virus (HIV)
  • Known active Hepatitis B or Hepatitis C
  • Received live attenuated vaccines within 30 days prior to start of study treatment. Patients must also agree to avoid live attenuated vaccines during study treatment.
  • Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic or immunosuppressive agents. Subjects with vitiligo, diabetes Type I, or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators, inhaled steroids, or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjøgren's syndrome will not be excluded from the study.
  • Known contraindications to BCG, defined as one of the following:
  • History of systemic hypersensitivity reaction or history of febrile systemic BCG reaction
  • Febrile illness or persistent gross hematuria
  • Active tuberculosis
  • Immunosuppression due to congenital or acquired immune deficiency, concurrent immune suppressive disease, systemic cancer therapy, or chronic immunosuppressive therapy other than topical or inhaled corticosteroids

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

United States7 sites

  • Memorial Sloan Kettering Basking Ridge (All Protocol Activities)

    Basking Ridge, New Jersey, 10065

  • Memorial Sloan Kettering Commack (All protocol activities)

    Commack, New York, 11725

  • Memorial Sloan Kettering West Harrison (All Protocol Activities)

    Harrison, New York, 10604

  • Memorial Sloan Kettering Monmouth (All Protocol Activities)

    Middletown, New Jersey, 07748

  • Memorial Sloan Kettering Bergen (All protocol activities)

    Montvale, New Jersey, 07645

  • Memorial Sloan Kettering Cancer Center (All Protocol Activities)

    New York, New York, 10065

  • Memorial Sloan Kettering Nassau (All Protocol Activities)

    Uniondale, New York, 11553

Other trials in United States

About this study

Official title: Phase II Study of Pembrolizumab (MK-3475) and Bacillus Calmette-Guérin (BCG) as First-Line Treatment for High-Risk T1 Non-Muscle- Invasive Bladder Cancer (NMIBC) and High- Grade Non-Muscle- Invasive Upper Tract Urothelial Cell Carcinoma (NMI-UTUCC)

The purpose of this study is to find out the effectiveness of pembrolizumab in combination with BCG as a first line therapy for participants with high grade T1 bladder cancer who are at "high risk" for BCG alone to be ineffective and are seeking an alternative treatment option to radical cystectomy. There is biologic rationale for combining pembrolizumab and BCG as two distinct immunotherapies with possible additive or synergistic activity in urothelial cancer. The combination of pembrolizumab with BCG will also be evaluated in an exploratory cohort of patients with upper tract urothelial cancer.

Read the detailed description

Patients will receive pembrolizumab (MK-3475) administered after TUR in combination with BCG as initial therapy. Pembrolizumab (MK-3475) will be administered as a 400 mg IV infusion at 6-week intervals (Q6W) for 9 doses over a 48 week period, unless there is unacceptable toxicity or other reasons that would warrant the discontinuation of treatment. Patients will receive once-weekly BCG therapy (TICE strain, 50 mg) for 6 consecutive weeks as a standard induction course, given as intravesical BCG for patients with T1 bladder cancer, and administered through a percutaneous nephrostomy tube in antegrade fashion for patients with high-grade NMI-UTUC, consistent with standard clinical practice. BCG will start on week 3 after the first infusion of pembrolizumab (400 mg) to allow for initial priming of T cells to further enhance the effects of BCG treatment. Initiation of induction BCG may be delayed (up to 14 days) if deemed clinically indicated by the treating physician due to side effects from TURBT or ureteroscopy and with permission from the Principal Investigator (PI).

Conditions
Bladder Cancer
Being tested
Pembrolizumab (MK-3475), Bacillus Calmette-Guérin (BCG)
Keywords
Pembrolizumab (MK-3475), Bacillus Calmette-Guérin (BCG), 17-602
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.

  • Pembrolizumab (MK-3475)Drug

    Pembrolizumab (MK-3475) will be administered as a 400 mg intravenous (IV) infusion at 6- week intervals for 9 doses over a 48-week.

  • Bacillus Calmette-Guérin (BCG)Drug

    Intravesical BCG will be administrated once per week over a 6-week period as induction therapy, followed by maintenance BCG consistent with standard clinical practice

Study groups in NCT03504163
Study groupRoleWhat they receive
High Risk T1 Bladder Cancer CohortExperimentalPts will receive pembrolizumab/MK-3475 after transurethral resection of bladder tumor/TURBT in comb w/BCG as initial therapy. Pembrolizumab (MK-3475) will be administered as a 400 mg IV infusion at 6-wk intervals for 9 doses over a 48-wk period, unless there is unacceptable toxicity or other reasons to discontinue treatment occur. Intravesical BCG therapy (TICE strain, 50 mg) will be given 1x-weekly for 6 consecutive wks as a standard induction course, followed by maintenance BCG consistent w/standard clinical practice. BCG will start on wk 3 after the first infusion of pembrolizumab (400 mg) to allow for initial priming of T cells to further enhance the effects of BCG treatment.
Receives: Drug: Pembrolizumab (MK-3475); Drug: Bacillus Calmette-Guérin (BCG)
Exploratory cohort for high-grade non-muscle-invasive upper tract urothelial carcinomaExperimentalPts will receive pembrolizumab (MK-3475) administered after ureteroscopy/laser ablation in comb w/BCG as initial therapy. Pembrolizumab (MK-3475) will be administered as 400 mg IV infusion at 6-week intervals for 9 doses over a 48-week period, unless there is unacceptable toxicity or other reasons that would warrant the discontinuation of treatment. Pts will receive once-weekly BCG therapy (TICE strain, 50 mg) for 6 consecutive wks as a standard induction course administered through a percutaneous nephrostomy tube in antegrade fashion for patients with high-grade NMI-UTUC, consistent with standard clinical practice. BCG will start on wk 3 after the first infusion of pembrolizumab (400 mg) to allow for initial priming of T cells to further enhance the effects of BCG treatment.
Receives: Drug: Pembrolizumab (MK-3475); Drug: Bacillus Calmette-Guérin (BCG)

What is being measured

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

  1. The proportion of patients who are disease-free

    The primary objective for the high-risk T1 bladder cohort is to estimate the proportion of patients who remain free from high-grade recurrence (by urine cytology, cystoscopy ± biopsy) at 6 months from the start of treatment with pembrolizumab (MK-3475) and BCG

    Measured: 6 months

Secondary outcomes (1)

  1. The proportion of patients who remain free from high-grade recurrence

    Determine the proportion of patients who remain free from high-grade recurrence (by urine cytology, cystoscopy ± biopsy) at 12 months from the start of treatment with pembrolizumab (MK-3475) and BCG

    Measured: 6 months

Timeline

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

  1. First posted20 Apr 2018
  2. Study start27 Jun 2018
  3. Primary completionApr 2027 (estimated)
  4. Study completionApr 2027 (estimated)

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
Non-randomised
Intervention model
Parallel groups
Model description
This is a phase II trial of Pembrolizumab (MK-3475) in combination with Bacillus Calmette-Guérin (BCG) as first-line therapy in patients with high-risk T1 bladder cancer and also in an exploratory cohort of patients with high-grade NMI-UTUC.
Masking
None (open label)
Enrolment
45 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03504163
Sponsor's protocol ID
17-602
Status last verified
Jul 2026
First submitted
11 Apr 2018
Last updated
17 Jul 2026
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pembrolizumab (MK-3475) and Bacillus Calmette-Guérin (BCG) in people with Bladder Cancer, run by Memorial Sloan Kettering Cancer Center at 7 sites in United States.

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 32 inclusion and 22 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: under way, not looking for participants, as of the sponsor's last update on 17 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

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?

This study is still under way. Results are not available in the source record yet.

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?

The proportion of patients who are disease-free (time frame: 6 months). 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 NCT03504163.

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 17 Jul 2026.

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