Clinical trial • Phase III • Oncology

PEMBROLIZUMAB for Muscle-invasive bladder cancer | Urothelial carcinoma

Phase III trial of PEMBROLIZUMAB for Muscle-invasive bladder cancer | Urothelial carcinoma.

Overview

Trial Therapeutic Area
Oncology
Trial Disease
Muscle-invasive bladder cancer | Urothelial carcinoma
Trial Stage
Phase III
Drug Modality
Monoclonal antibody | Small molecule

Key dates

Initial CTIS Submission Date
16-11-2023
First CTIS Authorization Date
08-01-2024

Trial design

Randomised, arm a: perioperative pembrolizumab (keytruda, pembrolizumab; product keytruda 25 mg/ml concentrate for solution for infusion; max recorded dose 200 mg) + neoadjuvant chemotherapy (cisplatin and gemcitabine as per protocol; gemcitabine maxdailydoseamount 1000 mg/m2, cisplatin maxdailydoseamount 70 [unit as recorded]). arm b (comparator): perioperative placebo (placebo to keytruda - normal saline solution) + neoadjuvant chemotherapy (cisplatin and gemcitabine as per protocol). detailed dosing schedules are not specified in the available ctis data.-controlled Phase III trial in Hungary, Belgium, Sweden and others.

Randomised
Yes
Comparator
Arm A: Perioperative pembrolizumab (KEYTRUDA, pembrolizumab; product KEYTRUDA 25 mg/mL concentrate for solution for infusion; max recorded dose 200 mg) + neoadjuvant chemotherapy (cisplatin and gemcitabine as per protocol; gemcitabine maxDailyDoseAmount 1000 mg/m2, cisplatin maxDailyDoseAmount 70 [unit as recorded]). Arm B (comparator): Perioperative placebo (Placebo to Keytruda - Normal Saline Solution) + neoadjuvant chemotherapy (cisplatin and gemcitabine as per protocol). Detailed dosing schedules are not specified in the available CTIS data.
Target Sample Size
404

Eligibility

Recruits 404 isVulnerablePopulationSelected: true. Informed consent is handled using subject information and informed consent form documents (L1_ICF_Main consent and related ICFs listed in documents). Consent is provided by the participant. No specific information on assent or consent for minors is provided in the available records..

Vulnerable Population
isVulnerablePopulationSelected: true. Informed consent is handled using subject information and informed consent form documents (L1_ICF_Main consent and related ICFs listed in documents). Consent is provided by the participant. No specific information on assent or consent for minors is provided in the available records.

Inclusion criteria

  • {"criterion_text":"- Have a histologically confirmed diagnosis of urothelial carcinoma (UC) / muscle invasive bladder cancer (MIBC) (T2-T4aN0M0 or T1-T4aN1M0) with predominant (≥50%) urothelial histology.\n- Have clinically non-metastatic bladder cancer (N≤1 M0) determined by imaging (computed tomography (CT) or magnetic resonance imaging (MRI)) of the chest/abdomen/pelvis.\n- Be deemed eligible for Radical Cystectomy (RC) + Pelvic Lymph Node Dissection (PLND).\n- Have Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.\n- Have adequate organ function.\n- Male and female participants are eligible to participate if they agree to the contraception use as per study protocol."}

Exclusion criteria

  • {"criterion_text":"- Has a known additional malignancy that is progressing or has required active anti-cancer treatment ≤3 years of study randomization with certain exceptions.\n- Has had an allogenic tissue/solid organ transplant.\n- Has received any prior systemic treatment for MIBC or non-invasive muscle bladder cancer (NMIBC - prior treatment for NMIBC with intravesical BCG/chemotherapy is permitted) or prior therapy with an anti- programmed cell death 1 (PD-1), anti-programmed cell death ligand 1/ ligand 2 (PD-L1/L2), or anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4).\n- Has ≥N2 disease or metastatic disease (M1) as identified by imaging.\n- Is cisplatin-ineligible, as defined by meeting any one of the cisplatin ineligibility criteria as per protocol.\n- Has received prior systemic anticancer therapy including investigational agents within 3 years of randomization or any radiotherapy to the bladder.\n- Has undergone partial cystectomy of the bladder to remove any NMIBC or MIBC.\n- Has received a live or live attenuated vaccine within 30 days before the first dose of study intervention.\n- Has a diagnosis of immunodeficiency or has a known history of human immunodeficiency virus (HIV) infection, Hepatitis B infection or known active Hepatitis C infection.\n- Has a known psychiatric or substance abuse disorder."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Event-Free Survival (EFS)","definition_or_measurement_approach":""}

Secondary endpoints

  • {"endpoint_text":"- Pathologic Complete Response (pCR) Rate","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Overall Survival (OS)","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Disease-Free Survival (DFS)","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Pathologic Downstaging (pDS) Rate","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Number of Participants Who Experienced an Adverse Event (AE)","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Number of Participants Who Discontinued Study Treatment Due to an AE","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Number of Participants Who Experienced Perioperative Complications","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Change in Patient-Reported Outcomes from Baseline in the Total Score of Functional Assessment of Cancer Therapy – General (FACT-G)","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Change in Patient-Reported Outcomes from Baseline in the Total Score of FACT-Bladder- (FACT-BI-Cys)","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Change in Patient-Reported Outcomes from Baseline in FACT-BI-Cys-Trial Outcome Index (TOI)","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Change in Patient-Reported Outcomes from Baseline in European Quality of Life Questionnaire (EQ-5D-5L) Visual Analog Score (VAS)","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Time to Deterioration (TTD) in the Total Score of FACT-G","definition_or_measurement_approach":""}
  • {"endpoint_text":"- TTD in EQ-5D-5L VAS","definition_or_measurement_approach":""}

Recruitment

Planned Sample Size
404
Recruitment Window Months
19
Consent Approach
Informed consent obtained using L1_ICF_Main consent and associated ICF documents (multiple language versions present: EN, ES, FR, DE, IT, HU, etc.). Consent provided by the participant; optional and supplementary consents (e.g., FBR consent, optional genetic consent) are available as separate ICF documents. No information on assent procedures or consent by legal guardians for minors is provided.

Methods

  • Recruitment materials and channels documented as recruitment arrangements, including: recruitment posters (K2_Recruitment Doc Poster in multiple countries/languages), patient brochures (K2_Recruitment Doc Patient Brochure), patient visit guides, master tissue brochure, and advertisements (country-specific recruitment documents are present in the documents list).
  • Subject information and informed consent forms (L1_ICF_Main consent and language-specific ICFs) used as part of recruitment and consent process.
  • Country-specific recruitment packs (K1/K2 recruitment documents) and patient-facing materials (posters, brochures) listed for France, Ireland, Germany, Hungary, Italy, Belgium, Spain, and others.

Geography

Total Number Of Sites
58
Total Number Of Participants
424

Hungary

Latest Decision Or Authorization Date
20-06-2025
Number Of Sites
6
Number Of Participants
45

Sites

Site Name
University Of Pecs
Department Name
Onkoterápiás Intézet
Contact Person Name
László Mangel
Contact Person Email
mangel.laszlo.study@pte.hu
Site Name
Gyor-Moson-Sopron Varmegyei Petz Aladar Egyetemi Oktato Korhaz
Department Name
Onkoradiológiai Osztály
Contact Person Name
András Szigeti
Contact Person Email
drszigetia.petz@gmail.com
Site Name
Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz-Rendelointezet
Department Name
Onkológiai Központ
Contact Person Name
Anikó Ragályi
Contact Person Email
szolnok.onkologia@gmail.com
Site Name
University Of Szeged
Department Name
Onkoterápiás klinika
Contact Person Name
Judit Oláh
Site Name
University Of Debrecen
Department Name
Klinikai Központ Onkológiai Klinika
Contact Person Name
Péter Árkosy
Contact Person Email
arkosy.peter@med.unideb.hu
Site Name
Bajcsy-Zsilinszky Korhaz Es Rendelointezet
Department Name
Onkológia Osztály
Contact Person Name
Erzsébet Lengyel
Contact Person Email
lengyel.erzsebet@bajcsy.hu

Belgium

Latest Decision Or Authorization Date
08-01-2024
Number Of Sites
5
Number Of Participants
41

Sites

Site Name
Jessa Ziekenhuis
Department Name
Algemeen Medische Oncologie
Contact Person Name
Daisy Luyten
Contact Person Email
daisy.luyten@jessazh.be
Site Name
CHU UCL Namur
Department Name
Medical Oncology
Contact Person Name
Lionel D'Hondt
Contact Person Email
lionel.dhondt@uclouvain.be
Site Name
Az Maria Middelares Gent
Department Name
Oncology Department
Contact Person Name
Christof Vulsteke
Contact Person Email
christof.vulsteke@azmmsj.be
Site Name
UZ Brussel
Department Name
Medische Oncologie
Contact Person Name
Sandrine Aspeslagh
Site Name
AZORG Campus Aalst-Moorselbaan
Department Name
Urology Department
Contact Person Name
Frederiek D'Hondt
Contact Person Email
frederiek.dhondt@olvz-aalst.be

Sweden

Latest Decision Or Authorization Date
19-02-2025
Number Of Sites
3
Number Of Participants
20

Sites

Site Name
Uppsala University Hospital
Department Name
KFUE Akademiska Sjukhuset Dag Hammarskjölds väg 8, Ingång 100/101
Contact Person Name
Anna Laurell
Contact Person Email
Anna.laurell@akademiska.se
Site Name
Region Vaesterbotten
Department Name
Norrlands universitetssjukhus, Daniel Naezéns väg, 907 37 Umeå, Cancercentrum
Contact Person Name
Camilla Thellenberg Karlsson
Contact Person Email
Camilla.thellenberg@umu.se
Site Name
Region Joenkoepings Laen
Department Name
Onkologmottagningen / KPE
Contact Person Name
Dimitrios Papantoniou
Contact Person Email
dimitrios.papantoniou@rjl.se

Denmark

Latest Decision Or Authorization Date
17-02-2025
Number Of Sites
2
Number Of Participants
12

Sites

Site Name
Odense University Hospital
Department Name
Onkologisk afdeling R
Contact Person Name
Niels Viggo Jensen
Contact Person Email
niels.viggo.jensen@rsyd.dk
Site Name
Herlev Hospital
Department Name
Onkologisk afdeling R
Contact Person Name
Lisa Sengeløv
Contact Person Email
lisa.sengeloev@umu.se

Poland

Latest Decision Or Authorization Date
24-02-2025
Number Of Sites
5
Number Of Participants
34

Sites

Site Name
Lux Med Onkologia Sp. z o.o.
Department Name
Oddział Onkologii Klinicznej i Chemioterapii
Contact Person Name
Jakub Żołnierek
Contact Person Email
adam.falkowski@luxmed.pl
Site Name
Europejskie Centrum Zdrowia Otwock Sp. z o.o.
Department Name
Szpital im. Fryderyka Chopina Oddział Onkologii Klinicznej i Chemioterapii
Contact Person Name
Cezary Szczylik
Contact Person Email
sekretariat@ecz-otwock.pl
Site Name
Uniwersytecki Szpital Kliniczny Im Jana Mikulicza Radeckiego We Wroclawiu
Department Name
Klinika Urologii i Onkologii Urologicznej
Contact Person Name
Anna Kołodziej
Contact Person Email
klu@usk.wroc.pl
Site Name
Centrum Onkologii Im. Prof. Franciszka Lukaszczyka W Bydgoszczy
Department Name
Ambulatorium Chemioterapii
Contact Person Name
Bogdan Żurawski
Site Name
Beskidzkie Centrum Onkologii Szpital Miejski Im. Jana Pawla II W Bielsku-Bialej
Department Name
Oddział Onkologiczny i Hematoonkologiczny
Contact Person Name
Marcin Kowalski
Contact Person Email
itatar@onkologia.bielsko.pl

Spain

Latest Decision Or Authorization Date
15-01-2024
Number Of Sites
10
Number Of Participants
81

Sites

Site Name
Hospital San Pedro De Alcantara
Department Name
Medical Oncology
Contact Person Name
Ricardo Collado Martin
Contact Person Email
porcupaintri1@yahoo.es
Site Name
Hospital Universitario La Paz
Department Name
Medical Oncology
Contact Person Name
Álvaro Pinto
Contact Person Email
alvaropintomarin@gmail.com
Site Name
Fundacion Instituto Valenciano De Oncologia
Department Name
Medical Oncology
Contact Person Name
María José Juan
Contact Person Email
mjuanfi81@hotmail.com
Site Name
Hospital Universitario Virgen De Valme
Department Name
Medical Oncology
Contact Person Name
Eva Fernández
Contact Person Email
evamfparra@yahoo.es
Site Name
Hospital Universitario Ramon Y Cajal
Department Name
Medical Oncology
Contact Person Name
Javier Molina
Contact Person Email
javier.molinace@gmail.com
Site Name
Hospital Universitario Quironsalud Madrid
Department Name
Medical Oncology
Contact Person Name
Elena Almagro
Contact Person Email
elena.almagro@quironsalud.es
Site Name
Hospital Del Mar
Department Name
Medical Oncology
Contact Person Name
Alejo Rodríguez
Contact Person Email
arodriguezvida@psmar.cat
Site Name
Hospital Universitari De Girona Doctor Josep Trueta
Department Name
Medical Oncology
Contact Person Name
Nuria Sala
Contact Person Email
nsgonzalez@iconcologia.net
Site Name
Hospital Clinico San Carlos
Department Name
Medical Oncology
Contact Person Name
Javier Puente
Contact Person Email
javierpuente.hcsc@gmail.com
Site Name
Hospital Universitario Virgen De ??? (site entries consolidated)
Department Name
Medical Oncology

Ireland

Latest Decision Or Authorization Date
17-02-2025
Number Of Sites
2
Number Of Participants
14

Sites

Site Name
Tallaght University Hospital
Department Name
Oncology Day Unit
Contact Person Name
Ray McDermott
Contact Person Email
ray.mcdermott@tuh.ie
Site Name
Cork University Hospital
Department Name
Oncology
Contact Person Name
Richard Bambury
Contact Person Email
richard.bambury@hse.ie

Germany

Latest Decision Or Authorization Date
14-04-2025
Number Of Sites
7
Number Of Participants
40

Sites

Site Name
Vivantes Netzwerk fuer Gesundheit GmbH
Department Name
Klinik für Urologie
Contact Person Name
Stefan Hinz
Contact Person Email
Stefan.Hinz@vivantes.de
Site Name
Universitaetsklinikum Erlangen AöR
Department Name
Urologische Klinik
Contact Person Name
Peter J. Goebell
Contact Person Email
peter.goebell@uk-erlangen.de
Site Name
Universitaetsklinikum Magdeburg AöR
Department Name
Klinik für Urologie, Uroonkologie, Robotergestützte und Fokale Therapie
Contact Person Name
Simon Blaschke
Contact Person Email
simon.blaschke@med.ovgu.de
Site Name
Universitaetsklinikum Tuebingen AöR
Department Name
Klinik für Urologie
Contact Person Name
Steffen Rausch
Site Name
Charite Universitaetsmedizin Berlin KöR
Department Name
Klinik für Urologie Campus Charité Mitte
Contact Person Name
Maria De Santis
Contact Person Email
maria.de-santis@charite.de
Site Name
Universitaetsklinikum Carl Gustav Carus Dresden
Department Name
Klinik und Poliklinik für Urologie
Contact Person Name
Katharina Böhm
Site Name
University Medical Centre Schleswig-Holstein
Department Name
Klinik für Urologie Campus Lübeck
Contact Person Name
Axel Merseburger / Melanie Klee
Contact Person Email
Melanie.Klee@UKSH.de

Italy

Latest Decision Or Authorization Date
24-06-2025
Number Of Sites
7
Number Of Participants
57

Sites

Site Name
IRCCS Istituto Nazionale Tumori Fondazione Pascale
Department Name
S.C. Oncologia Medica Uro-Ginecologica
Contact Person Name
Rosa Tambaro
Contact Person Email
r.tambaro@istitutotumori.na.it
Site Name
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Department Name
U.O.C. Oncologia Medica
Contact Person Name
Giampaolo Tortora
Site Name
Azienda Ospedaliero Universitaria Di Modena
Department Name
Oncologia Medica
Contact Person Name
Roberto Sabbatini
Contact Person Email
sabbatini@unimore.it
Site Name
Azienda Ospedaliero Universitaria Policlinico G Rodolico San Marco Di Catania
Department Name
S.C. Oncologia Medica
Contact Person Name
Hector Josè Soto Parra
Site Name
Fondazione IRCCS Istituto Nazionale Dei Tumori
Department Name
S.S. Oncologia Medica Genitourinaria
Contact Person Name
Elena Verzoni
Site Name
Azienda Ospedaliera S Maria Di Terni
Department Name
Oncologia Medica
Contact Person Name
Sergio Bracarda
Contact Person Email
s.bracarda@aospterni.it
Site Name
San Camillo Forlanini Hospital
Department Name
Oncologia Medica
Contact Person Name
Antonietta D'Alessio
Contact Person Email
adalessio@aospterni.it

France

Latest Decision Or Authorization Date
23-04-2026
Number Of Sites
11
Number Of Participants
80

Sites

Site Name
Centre Francois Baclesse
Department Name
Unité d'investigation clinique
Contact Person Name
Florence Joly-Lobbedez
Contact Person Email
f.joly@baclesse.unicancer.fr
Site Name
Institut De Cancerologie De L Ouest
Department Name
Service d'Oncologie
Contact Person Name
Sophie Abadie-Lacourtoisie
Site Name
Centre Leon Berard
Department Name
Unité Onco Urologie
Contact Person Name
Aude Flechon
Contact Person Email
aude.flechon@lyon.unicancer.fr
Site Name
Institut Sainte Catherine
Department Name
Oncology
Contact Person Name
Bertrand Billemont
Contact Person Email
b.billemont@isc84.org
Site Name
Hopital Prive Des Cotes D'armor
Department Name
Service Oncologie
Contact Person Name
Dominique Besson
Contact Person Email
d.besson@cario-sante.fr
Site Name
Clinique Victor Hugo
Department Name
Radiotherapy - oncology
Contact Person Name
Ossama Didas
Contact Person Email
essaisdidas@ilcgroupe.fr
Site Name
Hopitaux Prives De Metz
Department Name
Service d'Oncologie
Contact Person Name
Jerome Plaza
Contact Person Email
jerome.plaza@uneos.fr
Site Name
CHU De Rouen
Department Name
Service Urologie
Contact Person Name
Christian Pfister
Contact Person Email
christian.pfister@chu-rouen.fr
Site Name
Centre Hospitalier Universitaire De Montpellier
Department Name
Service Oncologie médicale
Contact Person Name
Delphine Topart
Contact Person Email
d-topart@chu-montpellier.fr
Site Name
Centre Jean Perrin
Department Name
Département d'oncologie médicale
Contact Person Name
Hakim Mahammedi
Site Name
Centre Leon Berard / additional French sites (consolidated)

Sponsor

Primary sponsor

Full Name
Merck Sharp & Dohme LLC
Organisation Type
Pharmaceutical company
Country Of Registered Address
United States

Contract research organisations

Name
Clario
Responsibilities
Central imaging: Blinded Independent Central Review eligibilty and VOP
Name
Almac Clinical Technologies LLC
Name
Parexel International Corp.
Responsibilities
EUB services (call center and medical services)
Name
IQVIA Laboratories LLC
Name
Iqvia Limited
Responsibilities
Laboratory Analysis: PD-L1, H&E Testing, pCR Analysis
Name
Signant Health LLC
Responsibilities
e-Data Capture: Electronic Reported-Outcomes for EQ-5D-5L, FACT-Bl-Cys and BCI
Name
Fortrea Inc.

Third parties

  • {"country":"United States","full_name":"Clario","duties_or_roles":"Central imaging: Blinded Independent Central Review eligibilty and VOP","organisation_type":"Industry"}
  • {"country":"United States","full_name":"Almac Clinical Technologies LLC","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Parexel International Corp.","duties_or_roles":"EUB services (call center and medical services)","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"IQVIA Laboratories LLC","duties_or_roles":"","organisation_type":"Industry"}
  • {"country":"United Kingdom","full_name":"Iqvia Limited","duties_or_roles":"Laboratory Analysis: PD-L1, H&E Testing, pCR Analysis","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Signant Health LLC","duties_or_roles":"e-Data Capture: Electronic Reported-Outcomes for EQ-5D-5L, FACT-Bl-Cys and BCI","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Fortrea Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
KEYTRUDA 25 mg/mL concentrate for solution for infusion
Active Substance
PEMBROLIZUMAB
Modality
Monoclonal antibody
Routes Of Administration
INTRAVENOUS INFUSION
Route
INTRAVENOUS INFUSION
Authorisation Status
Authorised (EU/1/15/1024/002)
Maximum Dose
200 mg
Investigational Product Name
GEMCITABINE
Active Substance
GEMCITABINE
Modality
Small molecule
Routes Of Administration
INTRAVENIOUS INFUSION
Route
INTRAVENOUS INFUSION
Maximum Dose
1000 mg/m2
Investigational Product Name
CISPLATIN
Active Substance
CISPLATIN
Modality
Small molecule
Routes Of Administration
INTRAVENIOUS INFUSION
Route
INTRAVENOUS INFUSION
Maximum Dose
70 (unit as recorded)
Investigational Product Name
Placebo to Keytruda - Normal Saline Solution
Modality
Other
Combination Treatment
Yes

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