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

Study Identifier:
057-12
CT.gov Identifier:
NCT02625961
EudraCT Identifier:
2014-004026-17
EU Trial (CTIS) Number:
2022-502526-41-00
Study Contact Information:
(210) 593-5651 or [email protected]
Recruitment Complete

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Study Summary

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

To hypothesize that the treatment with pembrolizumab will result in a clinically meaningful response in patients with high risk non-muscle-invasive bladder cancer

To evaluate the safety and tolerability of pembrolizumab among patients with HR NMIBC with CIS at baseline

To Evaluate the efficacy and safety results with extended minimum follow-up of 26.3 mo from KEYNOTE-057 cohort A.

To evaluate pts with BCG-unresponsive HR NMIBC with papillary tumors (no carcinoma in situ [C-IS]) who were ineligible for or declined radical cystectomy (RC).

In cohort C, to evaluate the efficacy and safety of coformulations of pembrolizumab and the LAG-3 inhibitor favezelimab or the TIGIT inhibitor vibostolimab are being evaluated in patients with BCG-unresponsive HR NMIBC with CIS ± papillary tumors.

Efficacy will be evaluated in patients who receive ≥1 dose of treatment and have a baseline evaluation consisting of pre-enrollment cystoscopy, TURBT/biopsy, urine cytology, and baseline CTU imaging. Safety and tolerability will be evaluated in patients who receive ≥1 dose of treatment.

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
  • Bladder
    • Phase
    The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
    II
    Sex
    Female & Male
    Age
    18 - 64 Years
    Study Drug
  • Drug: Experimental: Pembrolizumab
    • Read More
  • Drug: Experimental: Pembrolizumab coformulation
  • Drug: Biological: Favezelimab/pembrolizumab coformulation
  • Drug: ASCO 2016:
  • Drug: SITC 2016:
  • Drug: Patients with CIS or CIS plus papillary disease (Cohort A) (n=130) and patients with papillary disease without CIS (Cohort B) (n=130).
  • Drug: ASCO GU 2021:
  • Drug: Patients received pembro 200 mg every 3 wk for =35 cycles (~2 y).
  • Drug: Cohort C- Patients will be randomly assigned 1: 1 to receive the coformulation of pembrolizumab 200 mg and vibostolimab 200 mg or the coformulation of pembrolizumab 200 mg and favezelimab 800 mg intravenously every 3 weeks for ≤35 cycles or until central pathology-confirmed ≥T1 at any time point, persistent or recurrent CIS or high-grade Ta at 24-week efficacy review or thereafter, unacceptable toxicity, patient or physician decision to withdraw, or administrative reasons to discontinue
  • Drug: Patients received pembrolizumab 200 mg intravenously every 3 weeks for a maximum of 35 cycles.
    • Study Status
    Indicates the current recruitment status or the expanded access status
    Recruitment Complete

    Requirements information
    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 within 72 hours prior to receiving the first dose of study medication and be willing to use contraception in accordance with Section 5.7.2 of Protocol. and must be willing to use an adequate method of contraception
    • Male participants must be willing to use an adequate method of contraception
    • Be at least 18 years of age on day of signing informed consent
    • Unable or unwilling to undergo radical cystectomy
    • Key eligibility criteria include adults with histologically confirmed HR NMIBC (CIS ± high-grade Ta or T1 at baseline) that is BCG-unresponsive (persistent or recurrent CIS ± Ta/T1 ≤12 month of completing adequate BCG therapy) who are ineligible for or declined RC and have an ECOG PS of 0-2.
    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 / 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
    • 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

    Clinical Study Information for Healthcare Providers

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    Study Locations

    Location
    Investigator
    Status
    Condition(s) Treated at Site
    Location
    START Carolinas
    Myrtle Beach, SC, United States, 29572
    Investigator
    Neal Shore
    Status
    Recruitment Complete
    Condition(s) Treated at Site
    Bladder