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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04165317
Recruitment Status : Recruiting
First Posted : November 15, 2019
Last Update Posted : August 29, 2022
Sponsor:
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE November 13, 2019
First Posted Date  ICMJE November 15, 2019
Last Update Posted Date August 29, 2022
Actual Study Start Date  ICMJE December 30, 2019
Estimated Primary Completion Date June 3, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 27, 2021)
  • Event free survival (Cohort A: Arm A compared to Arm C) [ Time Frame: 55 months after first participant randomized ]
    Event free survival is defined as the time from randomization to date of EFS event.
  • Event free survival (Cohort A: Arm B compared to Arm C) [ Time Frame: 55 months after first participant randomized ]
    Event free survival is defined as the time from randomization to date of EFS event.
  • Complete response rate (Cohort B1) [ Time Frame: Registration to 12 months after last participant initially assessed ]
    Complete response (CR) rate defined as the proportion of participants in the analysis population with CR.
  • Event free survival (Cohort B2) [ Time Frame: Registration to 12 months after last participant initially assessed ]
    Event free survival is defined as the time from first dose to date of EFS event.
Original Primary Outcome Measures  ICMJE
 (submitted: November 13, 2019)
  • Event free survival (Arm A compared to Arm C) [ Time Frame: Randomization up to 55 months ]
    Event free survival is defined as the time from randomization to date of EFS event.
  • Event free survival (Arm B compared to Arm C) [ Time Frame: Randomization up to 55 months ]
    Event free survival is defined as the time from randomization to date of EFS event.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 18, 2022)
  • Overall Survival (Cohort A: Arm A compared to Arm C) [ Time Frame: Randomization up to 60 months from last participant randomized ]
    Overall survival is defined as the time from the date of randomization to the date of death due to any cause.
  • Overall Survival (Cohort A: Arm B compared to Arm C) [ Time Frame: Randomization up to 60 months from last participant randomized ]
    Overall survival is defined as the time from the date of randomization to the date of death due to any cause.
  • Complete response rate in participants with CIS at randomization (Cohort A: Arm A, B, C) [ Time Frame: Randomization up to 60 months from last participant randomized ]
    Complete response (CR) rate defined as the proportion of participants in the analysis population with CR.
  • Disease-specific survival (Cohort A: Arm A, B, C) [ Time Frame: Randomization up to 60 months from last participant randomized ]
    Disease specific survival (DSS) is defined as the time from randomization to death resulting from bladder cancer.
  • Health-related quality of life as measured by EORTC QLQ-C30 (European Organization for Treatment of Cancer Quality of Life Questionnaire for cancer patients) [ Time Frame: Randomization up to 60 months from last participant randomized ]
    EORTC QLQ-C30: included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting) and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties).
  • ctrough of PF-06801591 when in combination with BCG (induction and maintenance or induction). Cohort A: Arms A and B only. [ Time Frame: Randomization up to 24 months ]
    Ctrough will be summarized in Cohort A Arms A and B only.
  • Incidence of ADA/Nab of PF-06801591 when in combination with BCG (induction and maintenance or induction). Cohort A: Arms A and B only. [ Time Frame: Randomization up to 24 months ]
    Immunogenicity will be evaluated for Cohort A Arms A and B only.
  • Tumor sample biomarker status based on PD-L1 expression (high or low) [ Time Frame: Baseline ]
    Evaluate PD-L1 expression.
  • Duration of CR for participants with CIS at randomization [ Time Frame: Randomization/registration up to 60 months from last participant randomized ]
    Duration of CR is defined as time from first CR to first recurrence or death due to any cause, whichever occurs first.
  • Time to recurrence of low grade disease (Cohort A: Arm A, B, C) [ Time Frame: Randomization up to 60 months from last participant randomized ]
    Time to recurrence defined as time from randomization to the date of first documentation of recurrence of low grade disease or death due to any cause, whichever occurs first.
  • Time to cystectomy [ Time Frame: Randomization/registration to date of cystectomy (up to 5 years after last participant is randomized) ]
    Time to cystectomy is defined as time from randomization/registration to cystectomy in participants with NMIBC
  • Health-related quality of life as measured by PTAB (Patient Treatment Administration Burden Questionnaire) [ Time Frame: Randomization/registration up to 24 months ]
    PTAB is a 2-item PRO designed to assess, from the patient 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).
  • Percentage of Participants With All Causality and Treatment-related Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Withdrawals Due to TEAEs [ Time Frame: Baseline up to 60 months from the last participant randomized ]
    An adverse event (AE) is any untoward medical occurrence attributed to study drug in a participant who received study drug. AEs comprised both SAEs and non-SAEs. Causality assessment is made by the investigator. Grading is per the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Event (CTCAE) version 3.0.
  • Percentage of Participants With Laboratory Abnormalities [ Time Frame: Baseline up to 60 months from last participant randomized ]
    Percentage of participants with laboratory test abnormalities without regard to baseline abnormality. Grading is per the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Event (CTCAE) version 3.0.
  • Health-related quality of life as measured by EORTC QLQ-NMIBC24 (European Organization for Treatment of Cancer in patients with non-muscle invasion bladder cancer) [ Time Frame: Randomization/registration up to 60 months from the last participant randomized ]
    EORTC-QLQ-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).
  • Complete response rate at 12 months (Cohort B1) [ Time Frame: 12 months after last participant's initial assessment ]
    Complete response (CR) rate defined as the proportion of participants in the analysis population with CR at 12 months.
  • Event Free Survival (Cohort B1) [ Time Frame: Registration to 5 years after last participant randomized. ]
    Time from first dose to date of EFS event.
  • Overall Survival (Cohorts B1 and B2) [ Time Frame: Registration to 5 years after last participant randomized. ]
    Time from the date of first dose to the date of death due to any cause.
  • ctrough of PF-06801591 (Cohorts B1 and B2) [ Time Frame: Registration up to 24 months ]
    Ctrough will be summarized
  • Incidence of ADA/Nab of PF-06801591 (Cohorts B1 and B2) [ Time Frame: Registration up to 24 months ]
    Immunogenicity will be evaluated for participants with BCG unresponsive NMIBC, including those with CIS.
  • cmax of PF-06801591 (Cohort B2 only) [ Time Frame: Registration up to 24 months ]
    Cmax will be summarized in Cohort B2 only.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 13, 2019)
  • Overall Survival (Arm A compared to Arm C) [ Time Frame: Randomization up to 60 months from last participant randomized ]
    Overall survival is defined as the time from the date of randomization to the date of death due to any cause.
  • Overall Survial (Arm B compared to Arm C) [ Time Frame: Randomization up to 60 months from last participant randomized ]
    Overall survival is defined as the time from the date of randomization to the date of death due to any cause.
  • Complete response in participants with CIS at randomization [ Time Frame: Randomization up to 60 months from last participant randomized ]
    Number of CIS participants with complete response.
  • Disease-specific survival [ Time Frame: Randomization up to 60 months from last participant randomized ]
    Disease specific survival (DSS) is defined as the time from randomization to death resulting from bladder cancer.
  • Health-related quality of life as measured by EORTC QLQ-C30 (European Organization for Treatment of Cancer Quality of Life Questionnaire) [ Time Frame: Randomization up to 60 months from last participant randomized ]
    EORTC QLQ-C30: included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting) and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties).
  • ctrough of PF-06801591 when in combination with BCG (induction and maintenance or induction). Arms A and B only. [ Time Frame: Randomization up to 24 months ]
    Ctrough will be summarized in Arms A and B only.
  • ADAs; NAbs of PF-06801591 when in combination with BCG (induction and maintenance or induction). Arms A and B only. [ Time Frame: Randomization up to 24 months ]
    Immunogenicity will be evaluated for Arms A and B only.
  • Tumor sample biomarker status based on PD-L1 expression (high or low) [ Time Frame: Baseline ]
    Evaluate PD-L1 expression.
  • Duration of CR for participants with CIS at randomization [ Time Frame: Randomization up to 60 months from last participant randomized ]
    Duration of CR is defined as time from first CR to first recurrence or death due to any cause, whichever occurs first.
  • Time to recurrence of low grade disease [ Time Frame: Randomization up to 60 months from last participant randomized ]
    Time to recurrence defined as time from randomization to the date of first documentation of recurrence of low grade disease or death due to any cause, whichever occurs first.
  • Time to cystectomy [ Time Frame: Randomization to date of cystectomy (up to 5 years after last participant is randomized) ]
    Time to cystectomy is defined as time from randomization to cystectomy in participants with NMIBC
  • Health-related quality of life as measured by PTAB (Patient Treatment Administration Burden Questionnaire) [ Time Frame: Randomization up to 24 months ]
    PTAB is a 2-item PRO designed to assess, from the patient 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).
  • Percentage of Participants With All Causality and Treatment-related Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Withdrawals Due to TEAEs [ Time Frame: Baseline up to 60 months from the last participant randomized ]
    An adverse event (AE) is any untoward medical occurrence attributed to study drug in a participant who received study drug. AEs comprised both SAEs and non-SAEs. Causality assessment is made by the investigator. Grading is per the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Event (CTCAE) version 3.0.
  • Percentage of Participants With Laboratory Abnormalities [ Time Frame: Baseline up to 60 months from last participant randomized ]
    Percentage of participants with laboratory test abnormalities without regard to baseline abnormality. Grading is per the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Event (CTCAE) version 3.0.
  • Health-related quality of life as measured by EORTC QLQ-NMIBC24 [ Time Frame: Randomization up to 60 months from the last particpant randomized ]
    EORTC-QLQ-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).
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Sasanlimab in People With Non-muscle Invasive Bladder Cancer
Official Title  ICMJE 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
Brief 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 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.

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Non-muscle Invasive Bladder Cancer
Intervention  ICMJE
  • Drug: PF-06801591
    A monoclonal antibody (mAb) that blocks the interaction between PD-1 and PD-L1/PD-L2.
    Other Name: Sasanlimab
  • Drug: Bacillus Calmette-Guerin
    Immunotherapy treatment approved by FDA for patients with high-risk non-muscle invasive bladder cancer
    Other Name: BCG
Study Arms  ICMJE
  • Experimental: PF-06801591 + BCG induction and maintenance
    PF-06801591 in combination with Bacillus Calmette Guerin(induction+maintenance).
    Interventions:
    • Drug: PF-06801591
    • Drug: Bacillus Calmette-Guerin
  • Experimental: PF-06801591 + BCG induction only
    PF-06801591 in combination with Bacillus Calmette Guerin (induction only).
    Interventions:
    • Drug: PF-06801591
    • Drug: Bacillus Calmette-Guerin
  • Active Comparator: BCG induction and maintenance
    Bacillus Calmette Guerin (induction and maintenance).
    Intervention: Drug: Bacillus Calmette-Guerin
  • Experimental: BCG Unresponsive CIS
    PF-06801591
    Intervention: Drug: PF-06801591
  • Experimental: BCG Unresponsive NMIBC
    PF-06801591
    Intervention: Drug: PF-06801591
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 13, 2022)
1160
Original Estimated Enrollment  ICMJE
 (submitted: November 13, 2019)
999
Estimated Study Completion Date  ICMJE August 8, 2028
Estimated Primary Completion Date June 3, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Pfizer CT.gov Call Center 1-800-718-1021 ClinicalTrials.gov_Inquiries@pfizer.com
Listed Location Countries  ICMJE Australia,   Belgium,   Canada,   China,   France,   Germany,   Italy,   Japan,   Korea, Republic of,   Poland,   Russian Federation,   Spain,   United Kingdom,   United States
Removed Location Countries Portugal
 
Administrative Information
NCT Number  ICMJE NCT04165317
Other Study ID Numbers  ICMJE B8011006
2019-003375-19 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
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.
URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests
Current Responsible Party Pfizer
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Pfizer
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date August 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP