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.
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.
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.
Brief Title
A Study of Sasanlimab in People With Non-muscle Invasive Bladder Cancer
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.
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.
Categories
Completion Date
Completion Date Type
Estimated
Conditions
Non-muscle Invasive Bladder Cancer
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 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.
* 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.
Inclusion 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 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
* 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
Gender
All
Gender Based
false
Keywords
CREST
Sasanlimab
PF-06801591
Bacillus Calmette Guerin
BCG
Bladder cancer
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT04165317
Org Class
Industry
Org Full Name
Pfizer
Org Study Id
B8011006
Overall Status
Active, not recruiting
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
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
Primary Outcomes
Outcome Description
Event free survival is defined as the time from randomization to date of EFS event.
Outcome Measure
Event free survival (Cohort A: Arm A compared to Arm C)
Outcome Time Frame
55 months after first participant randomized
Outcome Description
Complete response (CR) rate defined as the proportion of participants in the analysis population with CR.
Outcome Measure
Complete response rate (Cohort B1) (Obsolete after stopping enrollment in Cohort B)
Outcome Time Frame
Registration to 12 months after last participant initially assessed
Outcome Description
Event free survival is defined as the time from first dose to date of EFS event.
Outcome Measure
Event free survival (Cohort B2) (Obsolete after stopping enrollment in Cohort B)
Outcome Time Frame
Registration to 12 months after last participant initially assessed
Secondary Ids
Secondary Id
CREST
Secondary Id
2023-509089-39-00
Secondary Outcomes
Outcome Description
Event free survival is defined as the time from randomization to date of EFS event.
Outcome Time Frame
55 months after first participant randomized
Outcome Measure
Event free survival (Cohort A: Arm B compared to Arm C)
Outcome Description
Overall survival is defined as the time from the date of randomization to the date of death due to any cause.
Outcome Time Frame
Randomization up to 60 months from last participant randomized
Outcome Measure
Overall Survival (Cohort A: Arm A compared to Arm C)
Outcome Description
Overall survival is defined as the time from the date of randomization to the date of death due to any cause.
Outcome Time Frame
Randomization up to 60 months from last participant randomized
Outcome Measure
Overall Survival (Cohort A: Arm B compared to Arm C)
Outcome Description
Complete response (CR) rate defined as the proportion of participants in the analysis population with CR.
Outcome Time Frame
Randomization up to 60 months from last participant randomized
Outcome Measure
Complete response rate in participants with CIS at randomization (Cohort A: Arm A, B, C)
Outcome Description
Disease specific survival (DSS) is defined as the time from randomization to death resulting from bladder cancer.
Outcome Time Frame
Randomization up to 60 months from last participant randomized
Outcome Measure
Disease-specific survival (Cohort A: Arm A, B, C)
Outcome Description
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).
Outcome Time Frame
Randomization up to 60 months from last participant randomized
Outcome Measure
Health-related quality of life as measured by EORTC QLQ-C30 (European Organization for Treatment of Cancer Quality of Life Questionnaire for cancer patients) (Obsolete for Cohort B after stopping enrollment)
Outcome Description
Ctrough will be summarized in Cohort A Arms A and B only.
Outcome Time Frame
Randomization up to 24 months
Outcome Measure
ctrough of PF-06801591 when in combination with BCG (induction and maintenance or induction). Cohort A: Arms A and B only.
Outcome Description
Immunogenicity will be evaluated for Cohort A Arms A and B only.
Outcome Time Frame
Randomization up to 24 months
Outcome Measure
Incidence of ADA/Nab of PF-06801591 when in combination with BCG (induction and maintenance or induction). Cohort A: Arms A and B only.
Outcome Description
Evaluate PD-L1 expression.
Outcome Time Frame
Baseline
Outcome Measure
Tumor sample biomarker status based on PD-L1 expression (high or low) (Obsolete for Cohort B after stopping enrollment)
Outcome Description
Duration of CR is defined as time from first CR to first recurrence or death due to any cause, whichever occurs first.
Outcome Time Frame
Randomization/registration up to 60 months from last participant randomized
Outcome Measure
Duration of CR for participants with CIS at randomization (Obsolete for Cohort B after stopping enrollment)
Outcome Description
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.
Outcome Time Frame
Randomization up to 60 months from last participant randomized
Outcome Measure
Time to recurrence of low grade disease (Cohort A: Arm A, B, C)
Outcome Description
Time to cystectomy is defined as time from randomization/registration to cystectomy in participants with NMIBC
Outcome Time Frame
Randomization/registration to date of cystectomy (up to 5 years after last participant is randomized)
Outcome Measure
Time to cystectomy (Obsolete for Cohort B after stopping enrollment)
Outcome Description
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).
Outcome Time Frame
Randomization/registration up to 24 months
Outcome Measure
Health-related quality of life as measured by PTAB (Patient Treatment Administration Burden Questionnaire) (Obsolete for Cohort B after stopping enrollment)
Outcome Description
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.
Outcome Time Frame
Baseline up to 60 months from the last participant randomized
Outcome Measure
Percentage of Participants With All Causality and Treatment-related Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Withdrawals Due to TEAEs (Obsolete for Cohort B after stopping enrollment)
Outcome Description
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.
Outcome Time Frame
Baseline up to 60 months from last participant randomized
Outcome Measure
Percentage of Participants With Laboratory Abnormalities (Obsolete for Cohort B after stopping enrollment)
Outcome Description
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).
Outcome Time Frame
Randomization/registration up to 60 months from the last participant randomized
Outcome Measure
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) (Obsolete for Cohort B after stopping enrollment)
Outcome Description
Complete response (CR) rate defined as the proportion of participants in the analysis population with CR at 12 months.
Outcome Time Frame
12 months after last participant's initial assessment
Outcome Measure
Complete response rate at 12 months (Cohort B1) (Obsolete after stopping enrollment in Cohort B)
Outcome Description
Time from first dose to date of EFS event.
Outcome Time Frame
Registration to 5 years after last participant randomized.
Outcome Measure
Event Free Survival (Cohort B1) (Obsolete after stopping enrollment in Cohort B)
Outcome Description
Time from the date of first dose to the date of death due to any cause.
Outcome Time Frame
Registration to 5 years after last participant randomized.
Outcome Measure
Overall Survival (Cohorts B1 and B2) (Obsolete after stopping enrollment in Cohort B)
Outcome Description
Ctrough will be summarized
Outcome Time Frame
Registration up to 24 months
Outcome Measure
ctrough of PF-06801591 (Cohorts B1 and B2) (Obsolete after stopping enrollment in Cohort B)
Outcome Description
Immunogenicity will be evaluated for participants with BCG unresponsive NMIBC, including those with CIS.
Outcome Time Frame
Registration up to 24 months
Outcome Measure
Incidence of ADA/Nab of PF-06801591 (Cohorts B1 and B2) (Obsolete after stopping enrollment in Cohort B)
Outcome Description
Cmax will be summarized in Cohort B2 only.
Outcome Time Frame
Registration up to 24 months
Outcome Measure
cmax of PF-06801591 (Cohort B2 only) (Obsolete after stopping enrollment in Cohort B)
See Also Links
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Benjamin Gartrell
Investigator Email
bgartrel@montefiore.org
Investigator Phone
718-405-8404