Efficacy and Safety of Pembrolizumab (MK-3475) in Combination With Chemoradiotherapy (CRT) Versus CRT Alone in Muscle-invasive Bladder Cancer (MIBC) (MK-3475-992/KEYNOTE-992)

Running, not enrolling · Phase 3 · Has a placebo group

Conditions studied: Urinary Bladder Neoplasms

In brief

Researchers are looking for new ways to treat muscle-invasive bladder cancer (MIBC). MIBC is a type of cancer that has not spread from the muscles in the bladder to other parts of the body. MIBC is treated by having surgery to remove the bladder (cystectomy). Not all people choose to have surgery and want to keep their bladder using other treatments. Chemoradiotherapy (CRT)- is a type of non-surgical treatment for MIBC which combines Chemotherapy (a treatment with medicine to destroy cancer cells or stop them growing) and Radiation therapy (a treatment that uses beams of intense energy \[like X-rays\] to shrink or get rid of tumors). Pembrolizumab is an immunotherapy, which is a treatment that helps the immune system fight cancer. A placebo looks like the study medicine but has no study medicine in it. Using a placebo helps researchers better understand if the study medicine works. The goal of this study is to learn: 1. If a study medicine pembrolizumab given with Chemoradiotherapy (CRT) can help people live longer without their cancer growing, spreading, or coming back compared to placebo given with CRT. 2. About the safety and how well people tolerate CRT alone or in combination with pembrolizumab.

Key facts

Study ID

NCT04241185

Run by

Merck Sharp & Dohme LLC

People needed

520

Starts

2020-05-19

Expected to finish

2031-11-01

Last updated by the study team

2026-05-01

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Has a histologically confirmed initial diagnosis of muscle-invasive bladder cancer (MIBC) with predominant urothelial histology
• Has clinically nonmetastatic bladder cancer (N0M0)
• Has planned and is eligible to receive chemoradiotherapy (CRT) and one of the protocol-specified radiosensitizing chemotherapy regimens
• Has Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
• Demonstrates adequate organ function
• Male participants are eligible to participate if they agree to the following during the intervention period and for at least 90 days after the last dose of CRT treatment:
• Refrain from donating sperm
• Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent; or must agree to use contraception unless confirmed to be azoospermic
• A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
• Is not a woman of childbearing potential (WOCBP)
• Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis), during the intervention period and for at least 180 days the time needed to eliminate each study intervention after the last dose of study intervention; and agrees not to donate eggs (ova, oocytes) to others or freeze/store for her own use for the purpose of reproduction during this period. The length of time required to continue contraception for each study intervention is as follows: MK-3475 - 120 days and CRT - 180 days

You may not qualify if…

• Has the presence of diffuse carcinoma in situ (CIS) (multiple foci of CIS) throughout the bladder
• Has the presence of urothelial carcinoma (UC) at any site outside of the urinary bladder in the previous 2 years except for Ta stage/T1 stage/CIS of the upper tract if the participant has undergone a complete nephroureterectomy
• Has a known additional malignancy that is progressing or has required active therapy within the past 3 years, except basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer or other carcinoma in situ that has undergone potentially curative therapy
• Has the presence of bilateral hydronephrosis
• Has limited bladder function with frequency of small amounts of urine (< 30 mL), urinary incontinence, or requires self-catheterization or a permanent indwelling catheter
• Has received prior pelvic/local radiation therapy for any reason or any antineoplastic treatment for muscle-invasive bladder cancer (MIBC). Treatment for non-muscle invasive bladder cancer (NMIBC) with intravesical instillation therapy that was completed ≥28 days prior to randomization is allowed. Prior systemic treatment of NMIBC is not permitted.
• Received prior therapy with an anti-PD-1 (programmed cell death protein 1), anti-PD-L1 (programmed death-ligand 1), or anti-PD-L2 (programmed cell death 1 ligand 2), or with an agent directed to another stimulatory or coinhibitory T-cell receptor (e.g., CTLA-4 [cytotoxic T-lymphocyte-associated protein 4], OX 40, or CD137 [cluster of differentiation 137])
• Has received a live vaccine within 30 days before the first dose of study medication
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study medication
• Has known severe hypersensitivity (≥Grade 3) to the selected chemotherapy regimen, and/or any of their excipients and excipients of pembrolizumab
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days before the first dose of study medication
• Has an active autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed
• Has a history of non-infectious pneumonitis that required steroids or has current pneumonitis
• Has an active infection requiring systemic therapy
• Has a known history of human immunodeficiency virus (HIV) infection
• Has a known history of hepatitis B or known active hepatitis C virus infection
• Has a known history of active tuberculosis (TB; Bacillus tuberculosis)
• Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study
• Has had an allogenic tissue/solid organ transplant

Where it is running

• Bay Pines VA Medical Center ( Site 0055) — Bay Pines, Florida, United States
• AdventHealth Orlando-AdventHealth Medical Group Hematology & Oncology at Orlandoc ( Site 0004) — Orlando, Florida, United States
• Norton Cancer Institute ( Site 0044) — Louisville, Kentucky, United States
• Pikeville Medical Center ( Site 0009) — Pikeville, Kentucky, United States
• Baltimore VA Medical Center ( Site 0054) — Baltimore, Maryland, United States
• Washington University ( Site 0003) — St Louis, Missouri, United States
• Summit Medical Group Cancer Center ( Site 6008) — Florham Park, New Jersey, United States
• John Theurer Cancer Center at Hackensack University Medical Center ( Site 0005) — Hackensack, New Jersey, United States
• New York Oncology Hematology P.C ( Site 0024) — Albany, New York, United States
• Roswell Park Cancer Institute ( Site 6009) — Buffalo, New York, United States
• Winthrop University Hospital ( Site 0069) — Mineola, New York, United States
• New York University Perlmutter Cancer Center ( Site 0001) — New York, New York, United States
• Westchester Medical Center ( Site 6014) — Valhalla, New York, United States
• Fairview Hospital-Moll Cancer Center ( Site 6013) — Cleveland, Ohio, United States
• Cleveland Clinic Main ( Site 0062) — Cleveland, Ohio, United States
• Cleveland Clinic - Hillcrest Hospital-Hillcrest Hospital Cancer Center ( Site 6012) — Mayfield Heights, Ohio, United States
• MidLantic urology ( Site 0070) — Bala-Cynwyd, Pennsylvania, United States
• Saint Francis Cancer Center ( Site 0026) — Greenville, South Carolina, United States
• Carolina Urologic Research Center ( Site 0002) — Myrtle Beach, South Carolina, United States
• Urology San Antonio Research ( Site 6010) — San Antonio, Texas, United States
• Inova Schar Cancer Institute ( Site 6006) — Fairfax, Virginia, United States
• West Virginia University - Charleston Area Medical Center ( Site 6003) — Charleston, West Virginia, United States
• Froedtert and Medical College of Wisconsin ( Site 0022) — Milwaukee, Wisconsin, United States
• Liverpool Hospital ( Site 0220) — Liverpool, New South Wales, Australia
• Washington Cancer Institute at MedStar Washington Hospital Center ( Site 0041) — Washington D.C., District of Columbia, United States

Full record on ClinicalTrials.gov

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