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BRIEF TITLE: 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)

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)

  • Org Study ID: 3475-992
  • Secondary ID: MK-3475-992,2019-004023-20,205383
  • NCT ID: NCT04241185
  • NCT Alias:
  • Sponsor: Merck Sharp & Dohme Corp. - Industry
  • Source: Merck Sharp & Dohme Corp.

Brief Summary

This study is designed to assess the antitumor efficacy and safety of pembrolizumab in combination with chemoradiotherapy (CRT) versus CRT alone in participants with muscle-invasive bladder cancer (MIBC). The primary hypothesis is that pembrolizumab + chemoradiotherapy is superior to placebo + chemoradiotherapy with respect to bladder intact event-free survival.

Overal Status Start Date Phase Study Type
Recruiting May 19, 2020 Phase 3 Interventional

Primary Outcomes:

Primary Outcome 1 - Measure: Bladder Intact Event-Free Survival (BI-EFS)

Primary Outcome 1 - Time Frame: Up to approximately 71 months


  • Urinary Bladder Neoplasms


Inclusion Criteria:

- Has a histologically confirmed diagnosis of MIBC with predominant urothelial histology

- Has clinically non-metastatic 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 180 days after the last dose of study

- 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 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

Exclusion Criteria:

- 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

- Has received prior pelvic/local radiation therapy 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 co-inhibitory 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 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 severe hypersensitivity (≥Grade 3) to pembrolizumab and/or the selected
chemotherapy regimen, and/or any of their excipients

- 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 prior to the first dose of study drug

- 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

- 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
Show More

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Official Information

Name: Medical Director

Role: Study Director

Affiliation: Merck Sharp & Dohme Corp.

Overall Contact

Name: Toll Free Number

Phone: 1-888-577-8839



Facility Status Contact
Norton Cancer Institute ( Site 0044)
Louisville, Kentucky 40207
United States
Recruiting Study Coordinator
Washington University ( Site 0003)
Saint Louis, Missouri 63110
United States
Recruiting Study Coordinator
New York Oncology Hematology P.C ( Site 0024)
Albany, New York 12206
United States
Recruiting Study Coordinator
Carolina Urologic Research Center ( Site 0002)
Myrtle Beach, South Carolina 29572
United States
Recruiting Study Coordinator
843-449-1010 ext. 257
Fakultni nemocnice Olomouc ( Site 0559)
Olomouc, 775 20
Recruiting Study Coordinator
2. LF UK a FN Motol ( Site 0555)
Praha 5, 150 06
Recruiting Study Coordinator
Nemocnice Na Bulovce ( Site 0556)
Praha 8, 180 81
Recruiting Study Coordinator
Herlev og Gentofte Hospital. ( Site 0401)
Herlev, Hovedstaden 2730
Recruiting Study Coordinator
Odense Universitetshospital ( Site 0403)
Odense, Syddanmark 5000
Recruiting Study Coordinator
North Estonia Medical Centre Foundation ( Site 0081)
Tallin, Harjumaa 13419
Recruiting Study Coordinator
Tartu University Hospital ( Site 0079)
Tartu, Tartumaa 51014
Recruiting Study Coordinator
Institut Sainte Catherine ( Site 0121)
Avignon, Provence-Alpes-Cote-d Azur 84918
Recruiting Study Coordinator
Centro Medico Integral de Cancerologia CEMIC ( Site 0144)
Salcaja, Quetzaltenango 09002
Recruiting Study Coordinator
Oncomedica ( Site 0145)
Guatemala, 01010
Recruiting Study Coordinator
Grupo Medico Angeles ( Site 0143)
Guatemala, 01015
Recruiting Study Coordinator
Medi-K Cayala ( Site 0142)
Guatemala, 01016
Recruiting Study Coordinator
Rambam Medical Center ( Site 0088)
Afula, HaTsafon 1834111
Recruiting Study Coordinator
Chaim Sheba Medical Center ( Site 0087)
Ramat Gan, Tel Aviv 5265601
Recruiting Study Coordinator
Sourasky Medical Center ( Site 0089)
Tel Aviv, Tell Abib 6423906
Recruiting Study Coordinator
Hadassah Medical Center. Ein Kerem ( Site 0086)
Jerusalem, 9112001
Recruiting Study Coordinator
AOU Careggi ( Site 0191)
Firenze, 50134
Recruiting Study Coordinator
Istituto Nazionale Tumori IRCCS Fondazione Pascale ( Site 0192)
Napoli, 80131
Recruiting Study Coordinator
Hirosaki University Hospital ( Site 0602)
Hirosaki, Aomori 036-8563
Recruiting Study Coordinator
University of Tsukuba Hospital ( Site 0605)
Tsukuba, Ibaraki 305-8576
Recruiting Study Coordinator
Medical Hospital, Tokyo Medical And Dental University ( Site 0601)
Tokyo, 113-8519
Recruiting Study Coordinator
National Cancer Center ( Site 0202)
Gyeonggi-do, Kyonggi-do 10408
Korea, Republic of
Recruiting Study Coordinator
Seoul National University Bundang Hospital ( Site 0204)
Seongnam-si, Kyonggi-do 13620
Korea, Republic of
Recruiting Study Coordinator
Chungnam National University Hospital ( Site 0203)
Daejeon, Taejon-Kwangyokshi 35015
Korea, Republic of
Recruiting Study Coordinator
Korea University Anam Hospital ( Site 0205)
Seoul, 02841
Korea, Republic of
Recruiting Study Coordinator
Severance Hospital Yonsei University Health System ( Site 0201)
Seoul, 03722
Korea, Republic of
Recruiting Study Coordinator
Asan Medical Center ( Site 0200)
Seoul, 05505
Korea, Republic of
Recruiting Study Coordinator
Pauls Stradins Clinical University Hospital ( Site 0073)
Riga, 1002
Recruiting Study Coordinator
Hospital Pulau Pinang ( Site 0239)
Penang, Pulau Pinang 10990
Recruiting Study Coordinator
Hospital Kuala Lumpur ( Site 0238)
Kuala Lumpur, 50586
Recruiting Study Coordinator
University Malaya Medical Centre ( Site 0236)
Kuala Lumpur, 59100
Recruiting Study Coordinator
Netherlands Cancer Institute (NKI) ( Site 0183)
Amsterdam, Noord-Holland 1066 CX
Recruiting Study Coordinator
CHLO, EPE - Hospital de Sao Francisco Xavier ( Site 0302)
Lisboa, 1449-005
Recruiting Study Coordinator
PAN American Center Oncologic ( Site 0280)
Rio Piedras, 00935
Puerto Rico
Recruiting Study Coordinator
Instituto Catalan de Oncologia - ICO ( Site 0103)
L Hospitalet De Llobregat, Barcelona 08908
Recruiting Study Coordinator
Hospital La Fe de Valencia ( Site 0105)
Valencia, Valenciana, Comunitat 46026
Recruiting Study Coordinator
National Cheng Kung University Hospital ( Site 0208)
Tainan, 704
Recruiting Study Coordinator
National Taiwan University Hospital ( Site 0210)
Taipei, 10002
Recruiting Study Coordinator
Taipei Veterans General Hospital ( Site 0211)
Taipei, 112
Recruiting Study Coordinator
Istanbul Uni. Cerrahpasa Tip Fakultesi ( Site 0501)
Istanbul, 34098
Recruiting Study Coordinator
Medeniyet Universitesi Tip Fakultesi Tibbi Onkoloji Bolumu ( Site 0504)
Istanbul, 34732
Recruiting Study Coordinator
Clinical oncology dispensary of Dnipro ( Site 0133)
Dnipro, Dnipropetrovska Oblast 49055
Recruiting Study Coordinator
Regional Oncology Center of Kharkiv ( Site 0134)
Kharkiv, Kharkivska Oblast 61000
Recruiting Study Coordinator
Ukranian Center of TomoTherapy ( Site 0140)
Kropyvnytskiy, Kirovohradska Oblast 25011
Recruiting Study Coordinator
National Cancer Institute of the MoH of Ukraine ( Site 0136)
Kyiv, Kyivska Oblast 03022
Recruiting Study Coordinator
Kyiv City Clinical Oncology Center ( Site 0135)
Kyiv, Kyivska Oblast 03115
Recruiting Study Coordinator