Study of Pembrolizumab (MK-3475) in Participants With High Risk Non-muscle Invasive Bladder Cancer (MK-3475-057/KEYNOTE-057)

Sponsor

Merck Sharp & Dohme LLC (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT02625961

Collaborator

(none)

260

Enrollment

Arm

89.6

Anticipated Duration (Months)

Study Details

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. The primary study hypothesis is that treatment with pembrolizumab will result in a clinically meaningful response.

Condition or Disease	Intervention/Treatment	Phase
Bladder Cancer	Biological: pembrolizumab	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

260 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase II Clinical Trial to Study the Efficacy and Safety of Pembrolizumab (MK-3475) in Subjects With High Risk Non-muscle Invasive Bladder Cancer (NMIBC) Unresponsive to Bacillus Calmette-Guerin (BCG) Therapy

Actual Study Start Date :

Feb 10, 2016

Anticipated Primary Completion Date :

Jul 26, 2022

Anticipated Study Completion Date :

Jul 30, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pembrolizumab Participants receive pembrolizumab, 200 mg, intravenously, every 3 weeks (Q3W) for up to 24 months.	Biological: pembrolizumab Other Names: MK-3475

Arm

Intervention/Treatment

Experimental: Pembrolizumab

Participants receive pembrolizumab, 200 mg, intravenously, every 3 weeks (Q3W) for up to 24 months.

Biological: pembrolizumab

Other Names:

MK-3475

Outcome Measures

Primary Outcome Measures

Complete Response Rate [Up to 3 years]
Disease Free Survival Rate [Up to 3 years]

Secondary Outcome Measures

Duration of Response [Up to 3 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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:

Muscle-invasive, locally advanced nonresectable, or metastatic urothelial carcinoma (i.e., T2, T3, T4, and / or stage IV)
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