Non-muscle Invasive Bladder CancerPhase 3CRESTNCT04165317
A Study of Sasanlimab in People With Non-muscle Invasive Bladder Cancer
A Phase 3 study testing PF-06801591 and Bacillus Calmette-Guerin in people with Non-muscle Invasive Bladder Cancer, run by Pfizer at 196 sites in 14 countries.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-muscle Invasive Bladder Cancer
- What is being tested?
- PF-06801591 and Bacillus Calmette-Guerin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,068 participants
- Where
- 196 sitesin 14 countries
- Study dates
- 30 Dec 2019to 2 Dec 2026
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
196 sites in 14 countries.
196 sites in 14 countries
United States44 sites
John H. Stroger, Jr. Hospital of Cook County
Chicago, Illinois, 60612
Urology Clinics of North Texas
Dallas, Texas, 75231
Baylor University Medical Center
Dallas, Texas, 75246
Urology Clinics of North Texas
Dallas, Texas, 75246
The Urology Center of Colorado
Denver, Colorado, 80211
Chesapeake Urology Research Associates
Hanover, Maryland, 21076
Urological Research Network Corp
Hialeah, Florida, 33016
Houston Metro Urology
Houston, Texas, 77027
Houston Methodist Hospital
Houston, Texas, 77030
UF Health Jacksonville
Jacksonville, Florida, 32209
UF Health North
Jacksonville, Florida, 32218
Koman Family Outpatient Pavilion
La Jolla, California, 92037
Sulpizio Cardiovascular Center at UC San Diego Health
La Jolla, California, 92037
UC San Diego Medical Center - La Jolla (Jacobs Medical Center / Thornton Pavilion)
La Jolla, California, 92037
UC San Diego Moores Cancer Center
La Jolla, California, 92093
DuPage Medical Group
Lisle, Illinois, 60532
Arkansas Urology
Little Rock, Arkansas, 72211
DuPage Medical Group Ambulatory Surgery Center
Lombard, Illinois, 60148
DuPage Medical Group
Lombard, Illinois, 60148
AUC Urologists LLC
Murrells Inlet, South Carolina, 29576
Carolina Urologic Research Center
Myrtle Beach, South Carolina, 29572
Parkway Surgery Center
Myrtle Beach, South Carolina, 29572
Atlantic Urology Clinics South Strand Office
Myrtle Beach, South Carolina, 29588.
Edward Hospital
Naperville, Illinois, 60540
Bellevue Hospital
New York, New York, 10016
Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
New York, New York, 10016
NYU Langone Medical Center (Tisch Hospital)
New York, New York, 10016
NYU Langone Health Urology Associates
New York, New York, 10017
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
Mount Sinai Hospital
New York, New York, 10029
Sentara Norfolk General Hospital
Norfolk, Virginia, 23507
University of California Irvine Medical Center
Orange, California, 92868
VA Portland Healthcare System
Portland, Oregon, 97239
Premier Medical Group of the Hudson Valley PC
Poughkeepsie, New York, 12603
Urology San Antonio PA
San Antonio, Texas, 78229
UC San Diego Medical Center - Hillcrest
San Diego, California, 92103
Ochsner LSU Health Shreveport - Regional Urology
Shreveport, Louisiana, 71106
Associated Medical Professionals of New York, PLLC
Syracuse, New York, 13210
Montefiore Medical Center - Montefiore Medical Park
The Bronx, New York, 10461
Montefiore Medical Center - Oncology Investigational Services
The Bronx, New York, 10461
Michigan Institute of Urology, PC
Troy, Michigan, 48084
Arizona Urology Specialists
Tucson, Arizona, 85741
Chesapeake Regional Surgery Center - Virginia Beach
Virginia Beach, Virginia, 23462
Urology of Virginia, PLLC
Virginia Beach, Virginia, 23462
China22 sites
Beijing Chao-yang Hospital
Beijing, Beijing Municipality, 100020
Peking University First Hospital
Beijing, Beijing Municipality, 100034
Beijing Cancer Hospital
Beijing, Beijing Municipality, 100142
Peking Union Medical College Hospital
Beijing, Beijing Municipality, 100730
Hunan Cancer Hospital
Changsha, Hunan, 410013
West China Hospital of Sichuan University
Chengdu, Sichuan, 610041
Chongqing University Cancer Hospital
Chongqing, 400030
Fujian Medical University Affiliated First Hospital
Fuzhou, Fujian, 350005
Zhejiang Provincial People's Hospital
Hangzhou, Zhejiang, 310014
The First Affiliated Hospital of Anhui Medical University
Hefei, Anhui, 230022
The First Affiliated Hospital of Nanchang University
Nanchang, Jiangxi, 330006
Nanjing Drum Tower Hospital
Nanjing, Jiangsu, 210008
Nantong Tumor Hospital
Nantong, Jiangsu, 226000
Ningbo First Hospital
Ningbo, Zhejiang, 315010
Fudan University Cancer Hospital
Shanghai, 200032
Fudan University Shanghai Cancer Center
Shanghai, 201321
Second Affiliated Hospital of Suzhou University
Suzhou, Jiangsu, 215004
The Second Hospital of Tianjin Medical University
Tianjin, 300211
The First Affiliated Hospital of Wenzhou Medical University
Wenzhou, Zhejiang, 325000
The First Affiliated Hospital of Wenzhou Medical University
Wenzhou, Zhejiang, 325035
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Wuhan, Hubei, 430022
First Affiliated Hospital of Xi 'an Jiaotong University
Xi'an, Shaanxi, 710061
Russia22 sites
Evimed Llc
Chelyabinsk, 454048
Regional Budgetary Healthcare Institution "Ivanovo Regional Oncology Dispensary"
Ivanovo, 153040
Ars Medika Center, LLC
Kaliningrad, 236006
Kaluga Regional Clinical Oncology Center
Kaluga, 248007
P.A. Hertsen Moscow Oncology Research Center- branch of the National Medical Research
Moscow, 125284
Federal Budgetary Institution of Healthcare "Privolzhsky District Medical Center of the Federal
Nizhny Novgorod, 603001
Federal Budgetary Institution of Healthcare "Privolzhsky District Medical Center of the Federal
Nizhny Novgorod, 603074
National Medical Research Radiological Center of the Ministry of Health of the Russian Federation
Obninsk, Kaluga Oblast, 249036
A.Tsyb Medical Research Radiological Center of the Ministry of Health of the Russian Federation
Obninsk, Kaluzhskaya OBL., 249036
BHI of Omsk region "Clinical Oncological Dispensary"
Omsk, 644013
Private Medical Institution "Euromedservice"
Pushkin, Sankt-Peterburg, 196603
Klinika UZI 4D, LLC
Pyatigorsk, Stavropolskiy KRAI, 357502
State Budgetary Institution of Ryazan Region "Regional Clinical Oncology Center"
Ryazan, 390011
Federal State Budgetary Healthcare Institution Saint - Petersburg
Saint Petersburg, 194017
Limited Liability Company "North-Western Medical Center"
Saint Petersburg, 194355
Hospital OrKli LLC
Saint Petersburg, 199178
State Budgetary Institution of Healthcare of the Republic of Mordovia
Saransk, Respublika Mordoviya, 430032
Federal State Budgetary Educational Institution of Higher Education
Saransk, 430005
Republican Clinical Oncology Dispensary of the Ministry of Health of Bashkortostan Republic
Ufa, 450054
Budgetary Healthcare Institution of Vologda region "Vologda Regional Clinical Hospital"
Vologda, 160002
Leningrad Regional Clinical Hospital
Vsevolozhskiy District, 188663
SBHI YaR Regional clinical oncology hospital
Yaroslavl, 150054
Spain19 sites
Complejo Hospitalario Universitario A Coruna
A Coruña, 15006
Hospital Universitari Germans Trias i Pujol
Badalona, Barcelona, 08916
Hospital del Mar
Barcelona, 08003
Fundacio Puigvert
Barcelona, 08025
Hospital de la Santa Creu i Sant Pau
Barcelona, 08041
Hospital San Pedro de Alcantara
Cáceres, 10003
Hospital Universitari de Girona Doctor Josep Trueta
Girona, 17007
Hospital General de Granollers
Granollers, Barcelona, 08402
Hospital Universitari de Bellvitge
L'Hospitalet de Llobregat, Barcelona, 08907
Hospital de Llíria
Llíria, 46160
Hospital Universitario Lucus Augusti
Lugo, 27003
Hospital Universitario de La Princesa
Madrid, 28006
Hospital Clínico San Carlos
Madrid, 28040
Hospital Universitario 12 de Octubre
Madrid, 28041
Hospital Universitario Puerta de Hierro Majadahonda
Majadahonda, Madrid, 28222
Complejo Hospitalario de Navarra
Pamplona, Navarre, 31008
Salut Sant Joan de Reus-Baix Camp
Reus, Tarragona, 43204
Fundacion Instituto Valenciano de Oncologia
Valencia, 46009
Hospital Arnau de Vilanova
Valencia, 46015
Italy16 sites
Azienda Unita Sanitaria Locale Toscana Sud-Est
Arezzo, 52100
Ospedale Area Aretina Nord - UOC Oncologia Medica
Arezzo, 52100
Ospedale San Donato
Arezzo, 52100
UO Oncologia Medica IRCCS Istituto Tumori "Giovanni Paolo II"
Bari, 70124
UO Oncologia, ASST di Cremona - Istituti Ospitalieri - Ospedale di Cremona
Cremona, CR, 26100
Ospedale Policlinico San Martino, IRCCS
Genova, 16132
Medical Oncology Unit, AO Papardo
Messina, 98158
IRCCS Ospedale San Raffaele, URI (Urological Research Institute)
Milan, 20132
Humanitas Istituto Clinico Catanese S.p.A - U.O. Oncologia Medica
Misterobianco (CT), Catania, 95045
Ospedale Generale Provinciale di Macerata - UOC Oncologia
Province of Macerata, 62100
Azienda USL IRCCS di Reggio Emilia
Reggio Emilia, RE, 42122
AUSL/IRCCS di Reggio Emilia
Reggio Emilia, 42123
IRCSS Istituto Clinico Humanitas - U.O. Oncologia Medica
Rozzano, Milano, 20089
Ordine Mauriziano Umberto I Hospital,
Turin, Other, 10128
AO Azienda Ospedaliera Ordine Mauriziano Di Torino
Turin, 10128
ASST Sette Laghi Ospedale di Circolo Fondazione Macchi
Varese, 21100
Canada14 sites
Centre integre universitaire de sante et de services sociaux (CIUSSS) du Saguenay-Lac-Saint-Jean
Chicoutimi, Quebec, G7H 5H6
Centre intégré universitaire de santé et de services sociaux (CIUSSS) du Saguenay-Lac-Saint-Jean
Chicoutimi, Quebec, G7H 7K9
Hamilton Regional Laboratory Medicine Program
Hamilton, Ontario, L8N 4A6
McMaster Institute of Urology/St Joseph's Healthcare Hamilton
Hamilton, Ontario, L8N 4A6
Kingston Health Sciences Center - Queen's University
Kingston, Ontario, K7L 2V7
Centre for Applied Urological Research
Kingston, Ontario, K7L 3J7
Kingston Health Sciences Centre -- Hotel Dieu Hospital
Kingston, Ontario, K7L 5G2
The Research Institute of the McGill University Health Centre
Montreal, Quebec, H3H 2R9
McGill University Health Centre
Montreal, Quebec, H4A 3J1
Hotel-Dieu de Quebec - CHU de Quebec - Universite Laval
Québec, Quebec, G1R 2J6
University Health Network , Toronto General Hospital
Toronto, Ontario, M5G 2C4
University Health Network
Toronto, Ontario, M5G 2C4
University Health Network - Princess Margaret Cancer Centre
Toronto, Ontario, M5G 2M9
Vancouver Prostate Centre at the Vancouver General Hospital
Vancouver, British Columbia, V5Z 1M9
Japan14 sites
National Hospital Organization Kyushu Cancer Center
Fukuoka, Fukuoka, 811-1395
Hamamatsu University Hospital
Hamamatsu, Shizuoka, 431-3192
Kagoshima University Hospital
Kagoshima, 890-8520
National Hospital Organization Kumamoto Medical Center
Kumamoto, 860-0008
National Hospital Organization Shikoku Cancer Center
Matsuyama, Ehime, 791-0280
Okayama Medical Center
Okayama, 701-1192
Osaka International Cancer Institute
Osaka, Osaka, 541-8567
Gunma Prefectural Cancer Center
Ōta, Gunma, 373-8550
Kindai University Hospital
Sakai, Osaka, 590-0197
National Hospital Organization Hokkaido Cancer Center
Sapporo, Hokkaido, 003-0804
Keio University Hospital
Shinjuku-ku, Tokyo, 160-8582
Ehime University Hospital
Tōon, Ehime, 791-0295
Yamagata University Hospital
Yamagata, 990-9585
Kanagawa cancer center
Yokohama, Kanagawa, 241-8515
France13 sites
Hôpital privé Antony (Pharmacy)
Antony, 92160
Hôpital Privé d'Antony
Antony, 92160
Clinique Belharra
Bayonne, 64100
CHU de Bordeaux Hôpital Pellegrin
Bordeaux, 33000
Clinique Saint-Augustin
Bordeaux, 33074
Institut Bergonié
Bordeaux, 33076
Cabinet Privé d'urologie
Brest, 29200
CHPB Keraudren
Brest, 29200
Groupe Vivalto Sante - Clinique Pasteur-Lanroze- CFRO
Brest, 29229
Polyclinique de Limoges Site Chenieux
Limoges, 87000
Polyclinique de Gentilly
Nancy, 54100
Hôpital Bichat - Claude-Bernard
Paris, 75877
Clinique Sainte Anne
Strasbourg, 67000
Poland11 sites
NZOZ AKMED Andrzej Kupilas
Gliwice, 44-121
Regionalny Szpital Specjalistyczny im. Dr. Wladyslawa Bieganskiego
Grudziądz, 86-300
Wojewódzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Łodzi
Łódż, Łódź Voivodeship, 93-513
Niepubliczny Zaklad Opieki Zdrowotnej Centrum Urologiczne Sp. z o.o.
Mysłowice, 41-400
Provita Profamilia
Piotrkow Trybunalski, 97-300
Clinical Research Center Spolka z ograniczona odpowiedzialnoscia MEDIC-R Spolka Komandytowa
Poznan, 60-848
Clinical Research Center Spolka z ograniczona odpowiedzialnoscia MEDIC-R Spolka Komandytowa
Poznan, 61-731
ETG Skierniewice
Skierniewice, 96-100
Provita 001
Warsaw, 02-647
Medical Concierge Centrum Medyczne
Warsaw, 02-798
Lexmedica
Wroclaw, 53-114
South Korea7 sites
Kyungpook National University Chilgok Hospital
Daegu, 41404
National Cancer Center
Goyang-si, Gyeonggi-do, 10408
Seoul National University Bundang Hospital
Seongnam-si, Gyeonggi-do, 13620
Seoul National University Hospital
Seoul, Seoul-teukbyeolsi [seoul], 03080
Korea University Anam Hospital
Seoul, 02841
Severance Hospital, Yonsei University Health System
Seoul, 03722
Samsung Medical Center
Seoul, 06351
Germany6 sites
Urologicum Duisburg
Duisburg, 47169
Klinikum der Goethe-Universitaet Frankfurt
Frankfurt, 60590
Universitaetsklinikum Muenster, Urologie
Münster, 48149
Studienpraxis Urologie
Nürtingen, 72622
Universitaetsklinikum Tuebingen, Radiologische Universitätsklinik
Tübingen, 72076
Universitaetsklinikum Tuebingen
Tübingen, 72076
United Kingdom4 sites
Barts Health NHS Trust - St. Bartholomew's Hospital
London, CITY of London, EC1A 7BE
Barts Health NHS Trust, of Royal London Hospital
London, E1 1FR
Imperial College Healthcare NHS Trust, of The Bays, St. Mary's Hospital
London, W2 1NY
Charing Cross Hospital
London, W6 8RF
Australia3 sites
Southern Highlands Cancer Centre
Bowral, New South Wales, 2576
Box Hill Hospital
Box Hill, Victoria, 3128
Chris O'Brien Lifehouse Hospital
Camperdown, New South Wales, 2050
About this study
Official title: 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.
Read more
- 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.
Read the 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.
- Conditions
- Non-muscle Invasive Bladder Cancer
- Being tested
- PF-06801591, Bacillus Calmette-Guerin
- Keywords
- CREST, Sasanlimab, PF-06801591, Bacillus Calmette Guerin, BCG, Bladder cancer
- Medical subject headings
- Non-Muscle Invasive Bladder Neoplasms, Urinary Bladder Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PF-06801591Drug
Also called Sasanlimab
A monoclonal antibody (mAb) that blocks the interaction between PD-1 and PD-L1/PD-L2.
Bacillus Calmette-GuerinDrug
Also called BCG
Immunotherapy treatment approved by FDA for patients with high-risk non-muscle invasive bladder cancer
| Study group | Role | What they receive |
|---|---|---|
| PF-06801591 + BCG induction and maintenance | Experimental | PF-06801591 in combination with Bacillus Calmette Guerin(induction+maintenance). Receives: Drug: PF-06801591; Drug: Bacillus Calmette-Guerin |
| PF-06801591 + BCG induction only | Experimental | PF-06801591 in combination with Bacillus Calmette Guerin (induction only). Receives: Drug: PF-06801591; Drug: Bacillus Calmette-Guerin |
| BCG induction and maintenance | Active comparator | Bacillus Calmette Guerin (induction and maintenance). Receives: Drug: Bacillus Calmette-Guerin |
| BCG Unresponsive CIS | Experimental | PF-06801591 Receives: Drug: PF-06801591 |
| BCG Unresponsive NMIBC | Experimental | PF-06801591 Receives: Drug: PF-06801591 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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 outcomes (19)
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.
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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].
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Nov 2019
- Study start30 Dec 2019
- Primary completion2 Dec 2024
- Study completion2 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Non-muscle Invasive Bladder CancerStudies of the same condition, open and under way.
- More trials run by PfizerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1,068 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pfizer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pfizer CT.gov Call Center, Study director, Pfizer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04165317
- Sponsor's protocol ID
- B8011006
- Other IDs
- CREST, 2023-509089-39-00, 2023
- Acronym
- CREST
- Status last verified
- Oct 2026
- First submitted
- 13 Nov 2019
- Last updated
- 15 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
Shore ND, Powles TB, Bedke J, Galsky MD, Redorta JP, 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 taken together with Bacillus Calmette-Guerin (BCG) compared with BCG alone in people with high-risk non-muscle invasive bladder cancer: a plain language summary. Future Oncol. 2026 Jun;22(13):1487-1499. doi: 10.1080/14796694.2026.2671256. Epub 2026 May 24.
PubMed 42177753Shore 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.
PubMed 40450141Steinberg 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.
PubMed 38189180