Study

Overview

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.

Study Type:

Interventional

Study Phase:

Phase 2

Estimated Enrollment:

320

Study Start Date:

February 2016

Estimated Study Completion Date:

August 2030

Estimated Primary Completion Date:

August 2026

Eligibility

Ages Eligible for Study:

18 years and older

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

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