Study of Sasanlimab (PF-06801591) in Combination With Bacillus Calmette-Guerin (BCG) in Participants With High-Risk Non-Muscle Invasive Bladder Cancer (CREST)

• ClinicalTrials.gov Identifier: NCT04165317
• Recruitment Status: Recruiting
• First Posted: November 15, 2019
• Last Update Posted: January 13, 2021
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: November 13, 2019
• First Posted Date: November 15, 2019
• Last Update Posted Date: January 13, 2021
• Actual Study Start Date: December 30, 2019
• Estimated Primary Completion Date: June 3, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 13, 2020)

• 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 Survival (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 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). Arms A and B only. [ Time Frame: Randomization up to 24 months ]
  Ctrough will be summarized in Arms A and B only.
• Incidence of ADA/Nab 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 (European Organization for Treatment of Cancer in patients with non-muscle invasion bladder cancer) [ Time Frame: Randomization 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).

Original Secondary Outcome Measures (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: Study of Sasanlimab (PF-06801591) in Combination With Bacillus Calmette-Guerin (BCG) in Participants With High-Risk Non-Muscle Invasive Bladder Cancer
• 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

Brief Summary

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

Phase 3 Design with 3 study Arms (A, B and C). Arms A and B consists of two study drugs, PF-06801591 plus BCG. Arm C consists of one study drug, BCG.

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Non-muscle Invasive Bladder Cancer

Intervention

• 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

• 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

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 13, 2019): 999
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2, 2026
• Estimated Primary Completion Date: June 3, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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 TURBT occurring within 12 weeks prior to randomization. A second TURBT must have been performed if indicated according to the current locally applicable guidelines, ie, American Urological Association, European Association of Urology

Exclusion Criteria:

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Pfizer CT.gov Call Center; 1-800-718-1021; ClinicalTrials.gov_Inquiries@pfizer.com

• Listed Location Countries: 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: NCT04165317
• Other Study ID Numbers: 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

• 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

• Responsible Party: Pfizer
• Study Sponsor: Pfizer
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: January 2021