A Study of Sasanlimab in People With Non-muscle Invasive Bladder Cancer (CREST)

A Phase 3, Multinational, Randomized, Open-Label, Three Parallel-Arm Study of PF-06801591, an Anti-PD-1 Antibody, in Combination With Bacillus Calmette-Guerin (BCG Induction With or Without BCG Maintenance) Versus BCG (Induction and Maintenance) in Participants With High-Risk, BCG-Naïve Non-Muscle Invasive Bladder Cancer or PF-06801591 as a Single Agent in Participants With BCG-Unresponsive NMIBC

The purpose of this study is to learn about the safety and effects of the study medicine (sasanlimab) in people with non-muscle invasive bladder cancer. This study is seeking participants whose bladder cancer is still in early stages, has not spread outside of the bladder, has been removed with surgery, and is high risk (Part A) or was previously treated with BCG (Bacillus Calmette Guerin), a standard treatment for bladder cancer (Part B).

In Part A (enrollment closed), each participant was assigned to one of three study treatment groups.

• One group is given sasanlimab and BCG at the study clinic.
• The second group is given sasanlimab and BCG at the study clinic. This group will receive BCG for the first six weeks only.
• The third group is given BCG only and will not receive sasanlimab.

In Part B of the study, each new participant will be assigned to a study treatment group based on the type of their bladder tumor.

- Both groups will be given sasanlimab at the study clinic.

On August 31, 2022, the Sponsor announced the discontinuation of enrollment to Part B. The decision to discontinue enrollment to Part B was not made for safety reasons.

Study Overview

• Status: Active, not recruiting
• Conditions: Non-muscle Invasive Bladder Cancer
• Intervention / Treatment: Drug: PF-06801591; Drug: Bacillus Calmette-Guerin

Detailed Description

CREST: Combination of sasanlimab and alternative BCG Regimens to Evaluate outcomes with Subcutaneous anti-PD-1 Treatment

Phase 3 Design with two Cohorts. Cohort A consists of 3 study Arms (A, B and C) of BCG naive participants. Arms A and B consist of two study drugs, PF-06801591 plus BCG. Arm C consists of one study drug, BCG. Cohort B consists of B1 and B2, which test PF-06801591 and include participants who have BCG unresponsive CIS (B1) or BCG unresponsive papillary only disease (B2).

The study is designed to demonstrate that PF-06801591 plus Bacillus Calmette Guerin (BCG) (induction and maintenance periods) is superior to BCG alone (induction and maintenance periods) in prolonging event free survival (EFS) in participants with high-risk naïve non-muscle invasive bladder cancer (NMIBC) and to demonstrate that PF-06801591 plus BCG (induction period only) is superior to BCG alone (induction and maintenance periods) in prolonging EFS in participants with high-risk NMIBC. The study is also designed to estimate the CR rate of PF-06801591 alone in participants with BCG unresponsive CIS and to evaluate the EFS of PF-06801591 alone in participants with BCG unresponsive NMIBC.

On August 31, 2022, the Sponsor announced the discontinuation of enrollment to Part B, which enrolled participants with BCG unresponsive NMIBC. The decision to discontinue enrollment to Part B was not made for safety reasons.

• Study Type: Interventional
• Enrollment (Actual): 1068
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Bowral, New South Wales, Australia, 2576
      • Southern Highlands Cancer Centre
    • Camperdown, New South Wales, Australia, 2050
      • Chris O'Brien Lifehouse Hospital
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • Box Hill Hospital
    • Box Hill, Victoria, Australia, 3128
      • Eastern Clinical Research Unit
    • Lilydale, Victoria, Australia, 3140
      • Yarra Ranges Health
• Belgium
  • Ghent, Belgium, 9000
    • UZ Gent
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Vancouver Prostate Centre at the Vancouver General Hospital
  • Ontario
    • Hamilton, Ontario, Canada, L8N 4A6
      • Hamilton Regional Laboratory Medicine Program
    • Kingston, Ontario, Canada, K7L 3J7
      • Centre for Applied Urological Research
    • Kingston, Ontario, Canada, K7L 5G2
      • Kingston Health Sciences Centre -- Hotel Dieu Hospital
    • Kingston, Ontario, Canada, K7L 2V7
      • Kingston Health Sciences Center - Queen's University
    • Toronto, Ontario, Canada, M5G 2C4
      • University Health Network
    • Toronto, Ontario, Canada, M5G 2M9
      • University Health Network - Princess Margaret Cancer Centre
    • Toronto, Ontario, Canada, M5G 2C4
      • University Health Network , Toronto General Hospital
  • Quebec
    • Chicoutimi, Quebec, Canada, G7H 5H6
      • Centre intégré universitaire de santé et de services sociaux (CIUSSS) du Saguenay-Lac-Saint-Jean
    • Chicoutimi, Quebec, Canada, G7H 7K9
      • Centre intégré universitaire de santé et de services sociaux (CIUSSS) du Saguenay-Lac-Saint-Jean
    • Montreal, Quebec, Canada, H4A 3J1
      • McGill University Health Centre
    • Montreal, Quebec, Canada, H3H 2R9
      • The Research Institute of the McGill University Health Centre
    • Québec, Quebec, Canada, G1R 2J6
      • Hotel-Dieu de Quebec - CHU de Quebec - Universite Laval
• China
  • Chongqing, China, 400030
    • Chongqing University Cancer Hospital
  • Shanghai, China, 200032
    • Fudan University Cancer Hospital
  • Shanghai, China, 201321
    • Fudan University Shanghai Cancer Center
  • Tianjin, China, 300211
    • The Second Hospital of Tianjin Medical University
  • Anhui
    • Hefei, Anhui, China, 230022
      • The First Affiliated Hospital of Anhui Medical University
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100142
      • Beijing Cancer Hospital
    • Beijing, Beijing Municipality, China, 100034
      • Peking University First Hospital
    • Beijing, Beijing Municipality, China, 100730
      • Peking Union Medical College Hospital
    • Beijing, Beijing Municipality, China, 100020
      • Beijing Chao-Yang Hospital
  • Fujian
    • Fuzhou, Fujian, China, 350005
      • Fujian Medical University Affiliated First Hospital
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
  • Hunan
    • Changsha, Hunan, China, 410013
      • Hunan Cancer Hospital
  • Jiangsu
    • Nanjing, Jiangsu, China, 210008
      • Nanjing Drum Tower Hospital
    • Nantong, Jiangsu, China, 226000
      • Nantong Tumor Hospital
    • Suzhou, Jiangsu, China, 215004
      • Second Affiliated Hospital of Suzhou University
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • The First Affiliated Hospital of Nanchang University
  • Shaanxi
    • Xi'an, Shaanxi, China, 710061
      • First Affiliated Hospital of Xi 'an Jiaotong University
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital of Sichuan University
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310014
      • Zhejiang Provincial People's Hospital
    • Ningbo, Zhejiang, China, 315010
      • Ningbo First Hospital
    • Wenzhou, Zhejiang, China, 325000
      • The First Affiliated Hospital of Wenzhou Medical University
    • Wenzhou, Zhejiang, China, 325035
      • The First Affiliated Hospital of Wenzhou Medical University
• France
  • Antony, France, 92160
    • Hôpital privé Antony (Pharmacy)
  • Bayonne, France, 64100
    • Clinique Belharra
  • Bordeaux, France, 33076
    • Institut Bergonie
  • Bordeaux, France, 33000
    • CHU de Bordeaux Hôpital Pellegrin
  • Bordeaux, France, 33074
    • Clinique Saint-Augustin
  • Brest, France, 29200
    • Cabinet Privé d'urologie
  • Brest, France, 29200
    • CHPB Keraudren
  • Brest, France, 29229
    • Groupe Vivalto Sante - Clinique Pasteur-Lanroze- CFRO
  • Limoges, France, 87000
    • Polyclinique de Limoges Site Chenieux
  • Nancy, France, 54100
    • Polyclinique de Gentilly
  • Paris, France, 75877
    • Hôpital Bichat - Claude-Bernard
  • Strasbourg, France, 67000
    • Clinique Sainte Anne
• Germany
  • Duisburg, Germany, 47169
    • Urologicum Duisburg
  • Frankfurt, Germany, 60590
    • Klinikum der Goethe-Universitaet Frankfurt
  • Münster, Germany, 48149
    • Universitaetsklinikum Muenster, Urologie
  • Nürtingen, Germany, 72622
    • Studienpraxis Urologie
  • Tübingen, Germany, 72076
    • Universitaetsklinikum Tuebingen
• Italy
  • Arezzo, Italy, 52100
    • Ospedale Area Aretina Nord - UOC Oncologia Medica
  • Arezzo, Italy, 52100
    • Ospedale San Donato
  • Arezzo, Italy, 52100
    • Azienda Unita Sanitaria Locale Toscana Sud-Est
  • Bari, Italy, 70124
    • UO Oncologia Medica IRCCS Istituto Tumori "Giovanni Paolo II"
  • Genova, Italy, 16132
    • IRCCS Azienda Ospedaliera Universitaria Policlinico San Martino Urologia
  • Macerata, Italy, 62100
    • Ospedale Generale Provinciale di Macerata - UOC Oncologia
  • Messina, Italy, 98158
    • Medical Oncology Unit, AO Papardo
  • Milan, Italy, 20132
    • IRCCS Ospedale San Raffaele, URI (Urological Research Institute)
  • Reggio Emilia, Italy, 42123
    • AUSL/IRCCS di Reggio Emilia
  • Turin, Italy, 10128
    • AO Azienda Ospedaliera Ordine Mauriziano Di Torino
  • Varese, Italy, 21100
    • ASST Sette Laghi Ospedale di Circolo Fondazione Macchi
  • CR
    • Cremona, CR, Italy, 26100
      • UO Oncologia, ASST di Cremona - Istituti Ospitalieri - Ospedale di Cremona
  • Catania
    • Misterobianco (CT), Catania, Italy, 95045
      • Humanitas Istituto Clinico Catanese S.p.A - U.O. Oncologia Medica
  • Milano
    • Rozzano, Milano, Italy, 20089
      • IRCSS Istituto Clinico Humanitas - U.O. Oncologia Medica
  • Other
    • Turin, Other, Italy, 10128
      • Ordine Mauriziano Umberto I Hospital,
  • RE
    • Reggio Emilia, RE, Italy, 42122
      • Azienda USL IRCCS di Reggio Emilia
• Japan
  • Kagoshima, Japan, 890-8520
    • Kagoshima University Hospital
  • Kumamoto, Japan, 860-0008
    • National Hospital Organization Kumamoto Medical Center
  • Okayama, Japan, 701-1192
    • Okayama Medical Center
  • Yamagata, Japan, 990-9585
    • Yamagata University Hospital
  • Ehime
    • Matsuyama, Ehime, Japan, 791-0280
      • National Hospital Organization Shikoku Cancer Center
    • Tōon, Ehime, Japan, 791-0295
      • Ehime University Hospital
  • Fukuoka
    • Fukuoka, Fukuoka, Japan, 811-1395
      • National Hospital Organization Kyushu Cancer Center
  • Gunma
    • Ōta, Gunma, Japan, 373-8550
      • Gunma Prefectural Cancer Center
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 003-0804
      • National Hospital Organization Hokkaido Cancer Center
  • Kanagawa
    • Yokohama, Kanagawa, Japan, 241-8515
      • Kanagawa Cancer Center
  • Osaka
    • Osaka, Osaka, Japan, 541-8567
      • Osaka International Cancer Institute
    • Sayama, Osaka, Japan, 589-8511
      • Kindai University Hospital
  • Shizuoka
    • Hamamatsu, Shizuoka, Japan, 431-3192
      • Hamamatsu University Hospital
  • Tokyo
    • Shinjuku-ku, Tokyo, Japan, 160-8582
      • Keio University Hospital
• Poland
  • Gliwice, Poland, 44-100
    • NZOZ AKMED Andrzej Kupilas
  • Grudziądz, Poland, 86-300
    • Regionalny Szpital Specjalistyczny im. Dr. Wladyslawa Bieganskiego
  • Mysłowice, Poland, 41-400
    • Niepubliczny Zaklad Opieki Zdrowotnej Centrum Urologiczne Sp. z o.o.
  • Piotrkow Trybunalski, Poland, 97-300
    • Provita Profamilia
  • Poznan, Poland, 61-731
    • Clinical Research Center Spolka Z Ograniczona Odpowiedzialnoscia Medic-R Spolka Komandytowa
  • Poznan, Poland, 60-848
    • Clinical Research Center Spolka Z Ograniczona Odpowiedzialnoscia Medic-R Spolka Komandytowa
  • Skierniewice, Poland, 96-100
    • ETG Skierniewice
  • Warsaw, Poland, 02-798
    • Medical Concierge Centrum Medyczne
  • Warsaw, Poland, 02-647
    • Provita 001
  • Wroclaw, Poland, 53-114
    • LexMedica
  • Łódź Voivodeship
    • Łódż, Łódź Voivodeship, Poland, 93-513
      • Wojewódzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Łodzi
• Russia
  • Chelyabinsk, Russia, 454048
    • Evimed Llc
  • Ivanovo, Russia, 153040
    • Regional Budgetary Healthcare Institution "Ivanovo Regional Oncology Dispensary"
  • Kaliningrad, Russia, 236006
    • Ars Medika Center, LLC
  • Kaluga, Russia, 248007
    • Kaluga Regional Clinical Oncology Center
  • Moscow, Russia, 125284
    • P.A. Hertsen Moscow Oncology Research Center- branch of the National Medical Research
  • Nizhny Novgorod, Russia, 603074
    • Federal Budgetary Institution of Healthcare "Privolzhsky District Medical Center of the Federal
  • Obninsk, Russia, 249036
    • National Medical Research Radiological Centre of the MoH of the Russian Federation
  • Omsk, Russia, 644013
    • BHI of Omsk region "Clinical Oncological Dispensary"
  • Ryazan, Russia, 390011
    • State Budgetary Institution of Ryazan Region "Regional Clinical Oncology Center"
  • Saint Petersburg, Russia, 194017
    • Federal State Budgetary Healthcare Institution Saint - Petersburg
  • Saint Petersburg, Russia, 194355
    • Limited Liability Company "North-Western Medical Center"
  • Saint Petersburg, Russia, 199178
    • Hospital OrKli LLC
  • Saransk, Russia, 4з0032
    • Federal State Budgetary Educational Institution of Higher Education
  • Ufa, Russia, 450054
    • Republican Clinical Oncology Dispensary of the Ministry of Health of Bashkortostan Republic
  • Vologda, Russia, 160002
    • Budgetary Healthcare Institution of Vologda region "Vologda Regional Clinical Hospital"
  • Vsevolozhskiy District, Russia, 188663
    • Leningrad Regional Clinical Hospital
  • Yaroslavl, Russia, 150054
    • SBHI YaR Regional clinical oncology hospital
  • Kaluzhskaya OBL.
    • Obninsk, Kaluzhskaya OBL., Russia, 249036
      • A.Tsyb Medical Research Radiological Center of the Ministry of Health of the Russian Federation
  • Respublika Mordoviya
    • Saransk, Respublika Mordoviya, Russia, 430032
      • State Budgetary Institution of Healthcare of the Republic of Mordovia
  • Sankt-Peterburg
    • Pushkin, Sankt-Peterburg, Russia, 196603
      • Private medical institution "Euromedservice"
  • Stavropolskiy KRAI
    • Pyatigorsk, Stavropolskiy KRAI, Russia, 357502
      • Klinika UZI 4D, LLC
• South Korea
  • Daegu, South Korea, 41404
    • Kyungpook National University Chilgok Hospital
  • Seoul, South Korea, 06351
    • Samsung Medical Center
  • Seoul, South Korea, 03722
    • Severance Hospital, Yonsei University Health System
  • Seoul, South Korea, 02841
    • Korea University Anam Hospital
  • Gyeonggi-do
    • Goyang-si, Gyeonggi-do, South Korea, 10408
      • National Cancer Center
    • Seongnam-si, Gyeonggi-do, South Korea, 13620
      • Seoul National University Bundang Hospital
  • Seoul-teukbyeolsi [seoul]
    • Seoul, Seoul-teukbyeolsi [seoul], South Korea, 03080
      • Seoul National University Hospital
• Spain
  • A Coruña, Spain, 15006
    • Complejo Hospitalario Universitario A Coruña
  • Barcelona, Spain, 08003
    • Hospital del Mar
  • Barcelona, Spain, 08041
    • Hospital De La Santa Creu I Sant Pau
  • Barcelona, Spain, 08025
    • Fundacio Puigvert
  • Cáceres, Spain, 10003
    • Hospital San Pedro de Alcantara
  • Girona, Spain, 17007
    • Hospital Universitari de Girona Doctor Josep Trueta
  • Llíria, Spain, 46160
    • Hospital de Llíria
  • Lugo, Spain, 27003
    • Hospital Universitario Lucus Augusti
  • Madrid, Spain, 28040
    • Hospital Clinico San Carlos
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28006
    • Hospital Universitario de La Princesa
  • Valencia, Spain, 46009
    • Fundación Instituto Valenciano de Oncología
  • Valencia, Spain, 46015
    • Hospital Arnau de Vilanova
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Hospital Universitari Germans Trias i Pujol
    • Granollers, Barcelona, Spain, 08402
      • Hospital General De Granollers
    • L'Hospitalet de Llobregat, Barcelona, Spain, 08907
      • Hospital Universitari de Bellvitge
  • Madrid
    • Majadahonda, Madrid, Spain, 28222
      • Hospital Universitario Puerta de Hierro Majadahonda
  • Navarre
    • Pamplona, Navarre, Spain, 31008
      • Complejo Hospitalario de Navarra
  • Tarragona
    • Reus, Tarragona, Spain, 43204
      • Salut Sant Joan de Reus-Baix Camp
• United Kingdom
  • London, United Kingdom, W6 8RF
    • Charing Cross Hospital
  • London, United Kingdom, E1 1FR
    • Barts Health NHS Trust, of Royal London Hospital
  • London, United Kingdom, W2 1NY
    • Imperial College Healthcare NHS Trust, of The Bays, St. Mary's Hospital
  • CITY of London
    • London, CITY of London, United Kingdom, EC1A 7BE
      • Barts Health NHS Trust - St. Bartholomew'S Hospital
• United States
  • Arizona
    • Tucson, Arizona, United States, 85741
      • Arizona Urology Specialists
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
      • Arkansas Urology
  • California
    • La Jolla, California, United States, 92093
      • UC San Diego Moores Cancer Center
    • La Jolla, California, United States, 92037
      • Koman Family Outpatient Pavilion
    • La Jolla, California, United States, 92037
      • Sulpizio Cardiovascular Center at UC San Diego Health
    • La Jolla, California, United States, 92037
      • UC San Diego Medical Center - La Jolla (Jacobs Medical Center / Thornton Pavilion)
    • Orange, California, United States, 92868
      • University of California Irvine Medical Center
    • San Diego, California, United States, 92103
      • UC San Diego Medical Center - Hillcrest
  • Colorado
    • Denver, Colorado, United States, 80211
      • The Urology Center of Colorado
  • Florida
    • Hialeah, Florida, United States, 33016
      • Urological Research Network Corp
    • Jacksonville, Florida, United States, 32209
      • UF Health Jacksonville
    • Jacksonville, Florida, United States, 32218
      • UF Health North
  • Illinois
    • Chicago, Illinois, United States, 60612
      • John H. Stroger, Jr. Hospital of Cook County
    • Lisle, Illinois, United States, 60532
      • DuPage Medical Group
    • Lombard, Illinois, United States, 60148
      • DuPage Medical Group Ambulatory Surgery Center
    • Lombard, Illinois, United States, 60148
      • DuPage Medical Group
    • Naperville, Illinois, United States, 60540
      • Edward Hospital
  • Louisiana
    • Shreveport, Louisiana, United States, 71106
      • Ochsner LSU Health Shreveport - Regional Urology
  • Maryland
    • Hanover, Maryland, United States, 21076
      • Chesapeake Urology Research Associates
  • Michigan
    • Troy, Michigan, United States, 48084
      • Michigan Institute of Urology, PC
  • New York
    • New York, New York, United States, 10016
      • Bellevue Hospital
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai
    • New York, New York, United States, 10029
      • Mount Sinai Hospital
    • New York, New York, United States, 10016
      • Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
    • New York, New York, United States, 10016
      • NYU Langone Medical Center (Tisch Hospital)
    • New York, New York, United States, 10017
      • NYU Langone Health Urology Associates
    • Poughkeepsie, New York, United States, 12603
      • Premier Medical Group of the Hudson Valley PC
    • Syracuse, New York, United States, 13210
      • Associated Medical Professionals of New York, PLLC
    • The Bronx, New York, United States, 10461
      • Montefiore Medical Center - Montefiore Medical Park
    • The Bronx, New York, United States, 10461
      • Montefiore Medical Center - Oncology Investigational Services
  • Oregon
    • Portland, Oregon, United States, 97239
      • VA Portland Healthcare System
  • South Carolina
    • Murrells Inlet, South Carolina, United States, 29576
      • AUC Urologists LLC
    • Myrtle Beach, South Carolina, United States, 29572
      • Carolina Urologic Research Center
    • Myrtle Beach, South Carolina, United States, 29572
      • Parkway Surgery Center
    • Myrtle Beach, South Carolina, United States, 29588.
      • Atlantic Urology Clinics South Strand Office
  • Texas
    • Dallas, Texas, United States, 75246
      • Baylor University Medical Center
    • Dallas, Texas, United States, 75231
      • Urology Clinics of North Texas
    • Dallas, Texas, United States, 75246
      • Urology Clinics of North Texas
    • Houston, Texas, United States, 77030
      • Houston Methodist Hospital
    • Houston, Texas, United States, 77027
      • Houston Metro Urology
    • San Antonio, Texas, United States, 78229
      • Urology San Antonio PA
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Sentara Norfolk General Hospital
    • Virginia Beach, Virginia, United States, 23462
      • Urology Of Virginia, Pllc
    • Virginia Beach, Virginia, United States, 23462
      • Chesapeake Regional Surgery Center - Virginia Beach

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histological confirmed diagnosis of high risk non-muscle invasive transitional cell carcinoma (TCC) of the urothelium of the urinary bladder (tumors of mixed transitional/non-transitional cell histology are allowed, but TCC must be the predominant histology)
• Complete resection of all Ta/T1 papillary disease (including participants with concurrent CIS), with most recent positive TURBT occurring within 12 weeks prior to randomization or study intervention. A second TURBT must have been performed if indicated according to the current locally applicable guidelines, ie, American Urological Association, European Association of Urology
• (Cohorts B1 and B2 only): Histological confirmed diagnosis of BCG-unresponsive high-risk, non-muscle invasive TCC of the urothelium within 12 months (CIS only) or 6 months (recurrent Ta/T1 disease) of completion of adequate BCG therapy.
• Have refused or are ineligible for radical cystectomy

Exclusion Criteria:

• Evidence of muscle-invasive, locally advanced or metastatic urothelial cancer or concurrent extravesical, non-muscle invasive TCC of the urothelium
• (Cohort A only): Intravesical BCG therapy within 2 years prior to randomization. Prior intravesical chemotherapy for NMIBC is allowed.

(Cohorts B1 and B2 only): Any systemic or intravesical chemotherapy or immunotherapy from the time of most recent positive TURBT to initiation of study intervention.

• Prior immunotherapy with anti PD-1, anti PD-L1, anti PD-L2, or anti cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody
• Prior treatment with immunostimulatory agents including interleukin (IL)-2, IL-15, interferon (INF)
• Prior radiation therapy to the bladder
• (Cohorts B1 and B2 only): Prior participation in Cohort A of this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PF-06801591 + BCG induction and maintenance; PF-06801591 in combination with Bacillus Calmette Guerin(induction+maintenance).	Drug: PF-06801591; A monoclonal antibody (mAb) that blocks the interaction between PD-1 and PD-L1/PD-L2.; Other Names: Sasanlimab; Drug: Bacillus Calmette-Guerin; Immunotherapy treatment approved by FDA for patients with high-risk non-muscle invasive bladder cancer; Other Names: BCG
Experimental: PF-06801591 + BCG induction only; PF-06801591 in combination with Bacillus Calmette Guerin (induction only).	Drug: PF-06801591; A monoclonal antibody (mAb) that blocks the interaction between PD-1 and PD-L1/PD-L2.; Other Names: Sasanlimab; Drug: Bacillus Calmette-Guerin; Immunotherapy treatment approved by FDA for patients with high-risk non-muscle invasive bladder cancer; Other Names: BCG
Active Comparator: BCG induction and maintenance; Bacillus Calmette Guerin (induction and maintenance).	Drug: Bacillus Calmette-Guerin; Immunotherapy treatment approved by FDA for patients with high-risk non-muscle invasive bladder cancer; Other Names: BCG
Experimental: BCG Unresponsive CIS; PF-06801591	Drug: PF-06801591; A monoclonal antibody (mAb) that blocks the interaction between PD-1 and PD-L1/PD-L2.; Other Names: Sasanlimab
Experimental: BCG Unresponsive NMIBC; PF-06801591	Drug: PF-06801591; A monoclonal antibody (mAb) that blocks the interaction between PD-1 and PD-L1/PD-L2.; Other Names: Sasanlimab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cohort A: Event Free Survival (EFS) as Assessed by the Investigator: Arm A Versus Arm C	EFS: time from randomization till recurrence of high-grade disease, progression of disease, persistence of carcinoma in situ (CIS), death due to any cause, whichever occurred first. Recurrence of high-grade disease: re-appearance of high-grade disease after randomization/study intervention initiation, re-appearance of high-grade disease after complete response (CR) for CIS participants or re-appearance of high-grade disease before CR for CIS participants and concurrent papillary disease at baseline. Progression of disease defined as any of following: Lamina propria invasion, muscle invasive disease, lymph node positive disease, metastatic disease, high-grade stage of bladder cancer (non-invasive papillary carcinoma [Ta] or invasion into the lamina propria without invasion into the muscularis propria [T1]) in participants with CIS only at baseline before achieving CR. Persistence of CIS: persistent CIS after induction, re-induction. EFS estimated using Kaplan-Meier analysis.	From randomization (Day 1) to first documentation of high-grade disease, progression of disease, persistence of CIS or death due to any cause, whichever occurred first (maximum follow up duration was up to 257.1 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cohort A: EFS as Assessed by the Investigator: Arm B Versus Arm C	EFS: time from randomization till recurrence of high-grade disease, progression of disease, CIS, death due to any cause, whichever occurred first. Recurrence of high-grade disease: re-appearance of high-grade disease after randomization/study intervention initiation, re-appearance of high-grade disease after CR for CIS participants or re-appearance of high-grade disease before CR for CIS participants and concurrent papillary disease at baseline. Progression of disease defined as any of following: Lamina propria invasion, muscle invasive disease, lymph node positive disease, metastatic disease, high-grade stage of bladder cancer (non-invasive papillary carcinoma [Ta] or invasion into the lamina propria without invasion into the muscularis propria [T1]) in participants with CIS only at baseline before achieving CR. Persistence of CIS: persistent CIS after induction, re-induction. EFS estimated using Kaplan-Meier analysis.	From randomization (Day 1) to the first documentation of high-grade disease, progression of disease, persistence of CIS or death due to any cause, whichever occurred first (maximum follow up duration was up to 257.1 weeks)
Cohort A: Overall Survival (OS) for Participants: Arm A Versus Arm C	Overall survival was defined as the time in months from the date of randomization to the date of death due to any cause. Participants last known to be alive will be censored at the date of last contact	From randomization (Day 1) until date of death due to any cause or censoring date
Cohort A: OS of Participants: Arm B Versus Arm C	Overall survival was defined as the time in months from the date of randomization to the date of death due to any cause. Participants last known to be alive will be censored at the date of last contact.	From randomization (Day 1) until date of death due to any cause or censoring date
Cohort A: Percentage of Participants With Complete Response (CR)as Assessed by Investigator: Participants With CIS at Baseline in Full Analysis Set	CR was defined as histologic disappearance of malignancy on bladder biopsy with negative cytology and cystoscopy or negative cytology and positive cystoscopy with biopsy-proven low-grade stage of bladder cancer defined as a non-invasive papillary carcinoma (Ta) lesion or non-malignant tissue for participants with CIS at randomization. 95% CI was based on Clopper-Pearson method.	From randomization (Day 1) to the first documented CR (maximum follow up duration was up to 257.1 weeks)
Cohort A: Duration of CR as Assessed by the Investigator: Participants With CIS at Baseline in Full Analysis Set	Duration of CR was defined as the time from the first documentation of CR to the date of an EFS event for participants with CR. EFS was defined as the time in months from randomization until recurrence of high-grade disease, progression of disease, persistence of CIS or death due to any cause, whichever occurred first. CR was defined as histologic disappearance of malignancy on bladder biopsy with negative cytology and cystoscopy or negative cytology and positive cystoscopy with biopsy-proven low-grade stage of bladder cancer defined as a non-invasive papillary carcinoma (Ta) lesion or non-malignant tissue for participants with CIS at randomization. Kaplan-Meier method was used. 95% CI was estimated based on Brookmeyer and Crowley method.	From date of first documentation of CR to date of an EFS event (maximum follow up duration was up to 257.1 weeks)
Cohort A: Time to Recurrence of Low-Grade Disease Assessed by the Investigator	Time to recurrence of low-grade disease was defined as the time from randomization to the date of first documentation of recurrence of low-grade disease. Recurrence of low-grade disease was defined as re-appearance of low-grade disease (low-grade Ta) after randomization based on positive biopsy, cystoscopy or cytology result. Kaplan-Meier method was used. 95% CI was estimated based on Brookmeyer and Crowley method.	From randomization (Day 1) to the date of positive biopsy, cystoscopy or cytology results (maximum follow up duration was up to 257.1 weeks)
Cohort A: Time to Cystectomy	Time to cystectomy was defined as time from randomization to cystectomy. Participants without a cystectomy will be censored at death date or last date known to be alive.	From randomization (Day 1) to date of cystectomy or censoring date
Cohort A: Disease Specific Survival (DSS) as Assessed by the Investigator	DSS was defined as the time from randomization to death resulting from bladder cancer, as assessed by the investigator. Participants last known to be alive will be censored at the date of last contact.	From randomization (Day 1) to the first documentation of death from bladder cancer
Cohort A: Number of Participants With Treatment Emergent Adverse Events (TEAEs)	An adverse event (AE) was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. TEAEs were those events with onset dates occurring during the on-treatment period. On-treatment period was defined as the time from the first dose of study treatment up to 30 days after last dose of study treatment or 1 day before start day of new anti-cancer therapy.	From first dose of study treatment (Day 1) up to 30 days after last dose of study treatment or 1 day before anti-cancer therapy
Cohort A: Number of Participants With Serious TEAEs	An adverse event (AE) was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. TEAEs were those events with onset dates occurring during the on-treatment period. On-treatment period was defined as the time from the first dose of study treatment up to 30 days after last dose of study treatment or 1 day before start day of new anti-cancer therapy. A serious adverse event (SAE) was any untoward medical occurrence at any dose that: resulted in death or was life threatening or required inpatient hospitalization or prolongation of existing hospitalization or resulted in persistent or significant disability/incapacity, resulted in congenital anomaly/birth defect or other events.	From first dose of study treatment (Day 1) up to 30 days after last dose of study treatment or 1 day before anti-cancer therapy
Cohort A: Number of Participants With Treatment Related TEAEs and Treatment Related SAEs	An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. TEAEs were those events with onset dates occurring during the on-treatment period. On-treatment period was defined as the time from the first dose of study treatment up to 30 days after last dose of study treatment or 1 day before start day of new anti-cancer therapy. A SAE was any untoward medical occurrence at any dose that: resulted in death or was life threatening or required inpatient hospitalization or prolongation of existing hospitalization or resulted in persistent or significant disability/incapacity resulted in congenital anomaly/birth defect or other events. Relatedness was based on the investigator's judgement.	From first dose of study treatment (Day 1) up to 30 days after last dose of study treatment or 1 day before anti-cancer therapy
Cohort A: Number of Participant With Grade 3 or 4 and Grade 5 TEAEs Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0	An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. TEAEs were those events with onset dates occurring during the on-treatment period. On-treatment period was defined as the time from the first dose of study treatment up to 30 days after last dose of study treatment or 1 day before start day of new anti-cancer therapy. NCI-CTCAE version 5.0, severity was graded as Grade 1: Mild, Grade 2: Moderate, Grade 3: Severe and Grade 4 Life threatening and Grade 5: Death.	From first dose of study treatment (Day 1) up to 30 days after last dose of study treatment or 1 day before anti-cancer therapy
Cohort A: Number of Participant With Laboratory Abnormalities as Based on Severity (as Graded by NCI CTCAE v5.0)	Laboratory parameters: hematocrit, hemoglobin, platelets, white blood cells, absolute neutrophil count, lymphocytes, monocytes, eosinophils, basophils, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, alkaline phosphatase, sodium, potassium, magnesium, chloride, total calcium and bilirubin, blood urea nitrogen, urea, creatinine, uric acid, glucose (non-fasted), albumin, phosphorus/phosphate, lipase, amylase, thyroid function test + reflex free thyroxine, free triiodothyronine, adrenocorticotropic hormone, international normalized ratio, partial thromboplastin time (PTT)/activated PTT, hepatitis B surface antigen, hepatitis C virus antibody. Severity grades per NCI-CTCAE v5.0: 1: Mild, 2: Moderate, 3: Severe, 4: Life threatening,5: Death.	From first dose of study treatment (Day 1) up to 30 days after last dose of study treatment or 1 day before anti-cancer therapy
Cohort A: Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Non-Muscle Invasive Bladder Cancer (QLQ-C) 30 Total Score	The EORTC QLQ-C30 was a 30 self-administered questionnaire, which comprised of 5 functional domain subscales (physical functioning subscale, a role functioning subscale, an emotional functioning subscale, a cognitive functioning subscale and a social functioning subscale), 3 symptom scale (fatigue, pain, nausea and vomiting), 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/QoL scale. All the scales and single-item measures range in score from 0 (poor functioning/no symptoms) to 100 (excellent functioning/greater degree of symptoms). Higher scores on functional domains indicated higher levels of functioning and higher scores on symptom scale/single items indicated greater presence of symptoms.	Baseline up to recurrence of high-grade disease or disease progression, consent withdrawal, lost to follow-up, or death
Cohort A: Change From Baseline in EORTC QLQ- Non-Muscle Invasive Bladder Cancer (NMIBC24) Total Score	The EORTC QLQ NMIBC24 is a PRO developed and tested by the EORTC group specifically for participants with non-muscle invasive bladder cancer. The NMIBC24 has 24 items which can be grouped into 6 subscales: urinary symptoms (7 items), malaise (2 items), future worries (4 items), bloating/flatulence (2 items), sexual functioning (2 items), and male sexual issues (2 items). The NMIBC24 also assesses intravesical treatment, female sexual issues, sexual intimacy, risk of contaminating a partner, and sexual enjoyment (1 item each). All of the subscales and single-item measures range in score from 0 (poor functioning/no symptoms) to 100 (excellent functioning/greater degree of symptoms). Higher scores indicate greater impairment, except for sexual function and sexual enjoyment items, where higher scores indicate better function.	Baseline up to recurrence of high-grade disease or disease progression, consent withdrawal, lost to follow-up, or death
Cohort A: Change From Baseline in Patient Treatment Administration Burden (PTAB) Questionnaire Total Score	The PTAB questionnaire was a 2-item PRO designed to assess, from the participant perspective, any pain associated with the treatment administration and the burden of the amount of time required to complete the treatment administration procedures (1 item each). The items were scored on a range of 0 to 4, where 0=no pain/ not at all burdensome and 4= extremely severe pain/ extremely burdensome.	Baseline up to 7 days after last dose of study treatment
Cohort A: Concentration at Trough (Ctrough) of PF-06801591 for Arms A and B Only	Concentration at Trough is defined as Predose/trough concentration Observed directly from data.	Pre-dose on Day 1 of Cycles 1, 2, 4, 6, 8, 10 and 13 (1 cycle=4 weeks)
Cohort A: Number of Participants With Positive (Anti-Drug Antibody) ADA or (Neutralizing Antibody) NAb: Arms A and B Only	A participant was considered ADA (or NAb) positive if (1) baseline titer was missing or negative and participant had >= 1 post-treatment positive titer (treatment-induced), or (2) positive titer at baseline and had a >= 4-fold dilution increase in titer from baseline in >= 1 post-treatment sample (treatment-boosted).	From start of study treatment (Day 1) until 7 days after last dose of study treatment (maximum up to 125.1 weeks and 104.4 weeks of treatment exposure for Arm A and Arm B, respectively)
Cohort A: Number of Participants According to Tumor Sample Biomarker Status Based on Baseline Programmed Cell Death Ligand 1 (PD-L1) Expression	PD-L1 expression was defined as the number of PD-L1 positive cells and/or qualitative assessment of PD-L1 staining on tumor and immune cells in regions of interest that were defined by tumor cell morphology. PDL-1 status was high if >=25% tumor cell or (immune cells present in the tumor area > 1% and PD-L1 positive immune cells+ >=25%) or (immune cells present in the tumor area = 1% and PD-L1 positive immune cells = 100%), and low if < 25% tumor cell and [(immune cells present in the tumor area > 1% and immune cells <25%) or (immune cells present in the tumor area = 1% and PD-L1 positive immune cells< 100%) or immune cells present = 0].	From start of study treatment (Day 1) until 7 days after last dose of study treatment (maximum up to 125.1 weeks, 104.4 weeks and 110 weeks of treatment exposure for Arm A, Arm B and Arm C, respectively)

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

General Publications

• Shore ND, Powles TB, Bedke J, Galsky MD, Palou Redorta J, Ku JH, Kretkowski M, Xylinas E, Alekseev B, Ye D, Guerrero-Ramos F, Briganti A, Kulkarni GS, Brinkmann J, Calella AM, Cesari R, Eccleston A, Michelon E, Vermette J, Wei C, Steinberg GD. Sasanlimab plus BCG in BCG-naive, high-risk non-muscle invasive bladder cancer: the randomized phase 3 CREST trial. Nat Med. 2025 Aug;31(8):2806-2814. doi: 10.1038/s41591-025-03738-z. Epub 2025 May 31.
• Steinberg GD, Shore ND, Redorta JP, Galsky MD, Bedke J, Ku JH, Kretkowski M, Hu H, Penkov K, Vermette JJ, Tarazi JC, Randall AE, Pierce KJ, Saltzstein D, Powles TB. CREST: phase III study of sasanlimab and Bacillus Calmette-Guerin for patients with Bacillus Calmette-Guerin-naive high-risk non-muscle-invasive bladder cancer. Future Oncol. 2024 May;20(14):891-901. doi: 10.2217/fon-2023-0271. Epub 2024 Jan 8.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): December 30, 2019
• Primary Completion (Actual): December 2, 2024
• Study Completion (Estimated): December 2, 2026

Study Registration Dates

• First Submitted: November 13, 2019
• First Submitted That Met QC Criteria: November 13, 2019
• First Posted (Actual): November 15, 2019

Study Record Updates

• Last Update Posted (Actual): January 22, 2026
• Last Update Submitted That Met QC Criteria: January 5, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Bladder cancer; BCG; CREST; Sasanlimab; PF-06801591; Bacillus Calmette Guerin
• Additional Relevant MeSH Terms: Urogenital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Urologic Neoplasms; Carcinoma; Urinary Bladder Diseases; Non-Muscle Invasive Bladder Neoplasms; Urinary Bladder Neoplasms; Biological Products; Complex Mixtures; Bacterial Vaccines; Vaccines; Tuberculosis Vaccines; BCG Vaccine
• Other Study ID Numbers: B8011006; CREST (Other Identifier: Alias Study Number); 2023-509089-39-00 (Registry Identifier: CTIS (EU))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No