Purpose

A global study to evaluate peri-operative pembrolizumab with chemotherapy versus placebo to pembrolizumab plus chemotherapy in cisplatin eligible patients.

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Have a histologically confirmed diagnosis of muscle invasive bladder cancer (T2-T4aN0M0) with predominant (≥50%) urothelial histology (histology and presence of muscle invasion to be confirmed by BICR): Participants with mixed histology are eligible provided the urothelial component is ≥50%.

Participants whose tumors contain any neuroendocrine component are not eligible.

Urothelial carcinomas not originating from the bladder (e.g., upper tract [ureters, renal pelvis], urethra) are not eligible.

- Have clinically non-metastatic bladder cancer (N0M0) determined by imaging (computed tomography (CT) chest or magnetic resonance imaging (MRI) of the abdomen/pelvis.

- Be deemed eligible for RC + PLND by his/her urologist and/or oncologist and agree to undergo curative intent standard RC + PLND (including prostatectomy if applicable).

- Have a transurethral resection (TUR) of a bladder tumor that is submitted and adequate to determine histology, muscle invasion, and PD-L1 status by central pathology vendor.

- Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

- Have demonstrated adequate organ function.

Exclusion Criteria

  • Has a known additional malignancy that is progressing or has required active anti-cancer treatment ≤3 years of study randomization with certain exceptions.
  • Has received any prior systemic anti-neoplastic treatment for MIBC.
  • Is cisplatin-ineligible, as defined by meeting any one of the study criteria.
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX-40, CD137).
  • Has received therapy with hematopoietic growth factor such as granulocyte-colony stimulating factor (G-CSF) or granulocyte-monocyte-colony stimulating factor(GM-CSF) in 14 days prior to randomization.
  • Has received prior systemic anti-cancer therapy including investigational agents within 3 years of randomization.
  • Has received any prior radiotherapy to the bladder.
  • Has received a live vaccine within 30 days prior to the first dose of study drug.
  • Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention.
  • Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug.
  • Has hypersensitivity to monoclonal antibodies (mAbs, including pembrolizumab) and/or any of their excipients.
  • Has severe hypersensitivity (≥Grade 3) to cisplatin and/or gemcitabine and any of their excipients.
  • Has an active autoimmune disease that has required systemic treatment in past 2 years
  • Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
  • Has an active infection requiring systemic therapy.

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description
Double-blind

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Pembrolizumab + Gemcitabine + Cisplatin + Surgery
Participants received 4 preoperative cycles of pembrolizumab PLUS gemcitabine PLUS cisplatin, followed by surgery, followed by up to 13 cycles of postoperative pembrolizumab.
  • Drug: Pembrolizumab
    Pembrolizumab 200 mg by intravenous (IV) infusion, given on Day 1 of each 21-day cycle
    Other names:
    • MK-3475
  • Drug: Gemcitabine
    Gemcitabine 1000 mg/m^2, IV infusion on Days 1 and 8 of each 21-day cycle
  • Drug: Cisplatin
    Cisplatin 70 mg/m^2, IV infusion on Day 1 of each 21-day cycle
  • Procedure: Surgery (radical cystectomy (RC) plus Pelvic Lymph Node Dissection [PLND])
    Surgical RC+PLND will be done in accordance with the American Urological Association (AUA)/American Society of Clinical Oncology (ASCO)/American Society for Radiation Oncology (ASTRO)/Society of Urologic Oncology (SUO) guidelines.
Placebo Comparator
Placebo + Gemcitabine + Cisplatin + Surgery
Participants received 4 preoperative cycles of placebo to pembrolizumab PLUS gemcitabine PLUS cisplatin, followed by surgery, followed by up to 13 cycles of postoperative placebo to pembrolizumab.
  • Drug: Gemcitabine
    Gemcitabine 1000 mg/m^2, IV infusion on Days 1 and 8 of each 21-day cycle
  • Drug: Cisplatin
    Cisplatin 70 mg/m^2, IV infusion on Day 1 of each 21-day cycle
  • Procedure: Surgery (radical cystectomy (RC) plus Pelvic Lymph Node Dissection [PLND])
    Surgical RC+PLND will be done in accordance with the American Urological Association (AUA)/American Society of Clinical Oncology (ASCO)/American Society for Radiation Oncology (ASTRO)/Society of Urologic Oncology (SUO) guidelines.
  • Drug: Placebo
    Placebo to pembrolizumab by IV infusion, given on Day 1 of each 21-day cycle

Recruiting Locations

Georgetown University Medical Center ( Site 0022)
Washington, District of Columbia 20007
Contact:
Study Coordinator
202-444-2198

More Details

NCT ID
NCT03924856
Status
Recruiting
Sponsor
Merck Sharp & Dohme Corp.

Study Contact

Toll Free Number
1-888-577-8839
Trialsites@merck.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.