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)

Summary

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.

Conditions

• Urinary Bladder Neoplasms

Interventions

DRUG

Pembrolizumab

400 mg of IV (intravenous) pembrolizumab once every 6 weeks.

RADIATION

Conventional Radiotherapy (Bladder only)

64 Gy of radiation administered to participant's bladder only. Thirty-two fractions will be administered over 6.5 weeks.

RADIATION

Conventional Radiotherapy (Bladder and pelvic nodes)

64 Gy of radiation administered to participant's bladder and pelvic nodes. Thirty-two fractions will be administered over 6.5 weeks.

RADIATION

Hypofractionated Radiotherapy (Bladder only)

55 Gy of radiation administered to participant's bladder only. Twenty fractions will be administered over 4 weeks.

DRUG

Cisplatin

35 mg of cisplatin per cubic meter of body volume, administered once weekly via IV infusion.

DRUG

Fluorouracil (5-FU)

5-FU administered via IV infusion at a dose of 500 mg per cubic meter of body volume on Days 1-5 and 22-26.

DRUG

Mitomycin C (MMC)

MMC administered via IV infusion at a dose of 12 mg per cubic meter of body volume on Day 1.

DRUG

Gemcitabine

Gemcitabine administered via IV infusion at a dose of 27 mg per cubic meter of body volume twice weekly.

DRUG

Placebo to Pembrolizumab

Placebo to intravenous (IV) pembrolizumab administered once every 6 weeks.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC

  lead INDUSTRY

Principal Investigators

• Medical Director · Merck Sharp & Dohme LLC

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2020-05-19

Primary Completion

2027-01-31

Completion

2031-11-01

FDA Drug

Yes

Countries

• United States
• Australia
• Chile
• Czechia
• Denmark
• Estonia
• France
• Guatemala
• Hungary
• Israel
• Italy
• Japan
• Latvia
• Malaysia
• Netherlands
• Poland
• Portugal
• Puerto Rico
• Romania
• South Korea
• Spain
• Taiwan
• Turkey (Türkiye)
• Ukraine
• United Kingdom

Study Locations