NCT04241185|Active Not RecruitingPhase 3DMCFDA Drug

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)

A Phase 3, Randomized, Double-blind, Placebo-controlled Clinical Trial to Study the Efficacy and Safety of Pembrolizumab (MK-3475) in Combination With Chemoradiotherapy (CRT) Versus CRT Alone in Participants With Muscle-invasive Bladder Cancer (MIBC) (KEYNOTE-992)

Merck Sharp & Dohme LLC ClinicalTrials.gov

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7 other identifiers

3475-992MK-3475-992205383U1111-1287-41902023-503500-87-00jRCT20802252872019-004023-20

Study Type

interventional

Target

520

Locations

24 countries

Sites

131

Timeline

RegisteredJan 2020

StartedMay 2020

CompletionNov 2031

Brief 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.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Strong global presence with extensive site network

Enrollment

520

participants targeted

Target at P75+ for phase_3

Timeline

66mo left

Started May 2020

Longer than P75 for phase_3

Geographic Reach

24 countries

131 active sites

Status

active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

11.5 years study duration

Study Progress52%

May 2020Nov 2031

First Submitted

Initial submission to the registry

January 22, 2020

Completed

5 days until next milestone

First Posted

Study publicly available on registry

January 27, 2020

Completed

4 months until next milestone

Study Start

First participant enrolled

May 19, 2020

Completed

6.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 31, 2027

Expected

4.8 years until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2031

Last Updated

May 1, 2026

Status Verified

April 1, 2026

Enrollment Period

6.7 years

First QC Date

January 22, 2020

Last Update Submit

April 29, 2026

Conditions

Urinary Bladder Neoplasms

Outcome Measures

Primary Outcomes (1)

Bladder Intact Event-Free Survival (BI-EFS)
BI-EFS is defined as the time from randomization to any of the following events: residual/recurrent MIBC post-chemoradiotherapy (CRT), nodal or distant metastases as assessed by computerized tomography (CT) and CT urography (CTU) or magnetic resonance urography (MRU) per blinded independent central review (BICR) and/or biopsy results assessed by central pathology review, radical cystectomy, or death due to any cause. If biopsy is not feasible due to participant safety, the imaging alone will be sufficient. The BI-EFS for all participants will be presented.
Up to approximately 76 months

Secondary Outcomes (10)

Overall Survival (OS)
Up to approximately 7 years
Metastasis-Free Survival (MFS)
Up to approximately 7 years
Time to Occurrence of Non-Muscle-Invasive Bladder Cancer (NMIBC)
Up to approximately 7 years
Number of Participants Who Experienced an Adverse Event (AE)
Up to approximately 7 years
Number of Participants Who Discontinued Study Intervention Due to an AE
Up to approximately 1 year
+5 more secondary outcomes

Study Arms (2)

Pembrolizumab + Chemotherapy + Radiotherapy

EXPERIMENTAL

Participants receive pembrolizumab plus one of three chemotherapy regimens chosen by investigator, plus one of three radiotherapy regimens chosen by investigator.

Drug: PembrolizumabRadiation: Conventional Radiotherapy (Bladder only)Radiation: Conventional Radiotherapy (Bladder and pelvic nodes)Radiation: Hypofractionated Radiotherapy (Bladder only)Drug: CisplatinDrug: Fluorouracil (5-FU)Drug: Mitomycin C (MMC)Drug: Gemcitabine

Placebo + Chemotherapy + Radiotherapy

PLACEBO COMPARATOR

Participants receive placebo to pembrolizumab plus one of three chemotherapy regimens chosen by investigator, plus one of three radiotherapy regimens chosen by investigator.

Radiation: Conventional Radiotherapy (Bladder only)Radiation: Conventional Radiotherapy (Bladder and pelvic nodes)Radiation: Hypofractionated Radiotherapy (Bladder only)Drug: CisplatinDrug: Fluorouracil (5-FU)Drug: Mitomycin C (MMC)Drug: GemcitabineDrug: Placebo to Pembrolizumab

Interventions

PembrolizumabDRUG

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

Also known as: MK-3475, KEYTRUDA®

Pembrolizumab + Chemotherapy + Radiotherapy

CisplatinDRUG

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