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)]

NCT03504163 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: 17-602
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 7

Brief 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. 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.

Conditions

Bladder Cancer

Keywords

Pembrolizumab (MK-3475); Bacillus Calmette-Guérin (BCG); 17-602

Outcome Measures

Primary Outcomes (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

  6 months

Secondary Outcomes (1)

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

  6 months

Study Arms (2)

High Risk T1 Bladder Cancer Cohort

EXPERIMENTAL

Pts 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.

Drug: Pembrolizumab (MK-3475); Drug: Bacillus Calmette-Guérin (BCG)

Exploratory cohort for high-grade non-muscle-invasive upper tract urothelial carcinoma

EXPERIMENTAL

Pts 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.

Drug: Pembrolizumab (MK-3475); Drug: Bacillus Calmette-Guérin (BCG)

Interventions

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.

Exploratory cohort for high-grade non-muscle-invasive upper tract urothelial carcinoma; High Risk T1 Bladder Cancer Cohort

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

Exploratory cohort for high-grade non-muscle-invasive upper tract urothelial carcinoma; High Risk T1 Bladder Cancer Cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (7)

Memorial Sloan Kettering Basking Ridge (All Protocol Activities)

Basking Ridge, New Jersey, 10065, United States

Location

Memorial Sloan Kettering Monmouth (All Protocol Activities)

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen (All protocol activities)

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Commack (All protocol activities)

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering West Harrison (All Protocol Activities)

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau (All Protocol Activities)

Uniondale, New York, 11553, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Study Officials

• Gopakumar Iyer, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: April 11, 2018
• First Posted: April 20, 2018
• Study Start: June 27, 2018
• Primary Completion: April 1, 2026
• Study Completion: April 1, 2026
• Last Updated: November 6, 2025

Record last verified: 2025-11

Locations

US (7)