Perioperative Pembrolizumab (MK-3475) Plus Neoadjuvant Chemotherapy Versus Perioperative Placebo Plus Neoadjuvant Chemotherapy for Cisplatin-eligible Muscle-invasive Bladder Cancer (MIBC) (MK-3475-866/KEYNOTE-866)
A global study to evaluate peri-operative pembrolizumab with chemotherapy versus placebo to pembrolizumab plus chemotherapy in cisplatin eligible patients.
- Urinary Bladder Cancer, Muscle-invasive
- Eligible Ages
- Over 18 Years
- Eligible Genders
- Accepts Healthy Volunteers
- 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.
- 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.
- Phase 3
- Study Type
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
- Masking Description
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.||
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.||
- Merck Sharp & Dohme Corp.
Study ContactToll Free Number