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

Pfizer

Status and phase: Active, not recruiting; Phase 3

Conditions: Non-muscle Invasive Bladder Cancer

Treatments: Drug: Bacillus Calmette-Guerin; Drug: PF-06801591

Study type: Interventional

Funder types: Industry

Identifiers

NCT04165317

2019-003375-19 (EudraCT Number)

2023-509089-39-00 (Registry Identifier)

CREST (Other Identifier)

B8011006

Details and patient eligibility

About

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.

Full 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.

Enrollment: 1,070 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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1,070 participants in 5 patient groups

PF-06801591 + BCG induction and maintenance

Experimental group

Description:

PF-06801591 in combination with Bacillus Calmette Guerin(induction+maintenance).

Treatment:

Drug: PF-06801591

Drug: Bacillus Calmette-Guerin

PF-06801591 + BCG induction only

Experimental group

Description:

PF-06801591 in combination with Bacillus Calmette Guerin (induction only).

Treatment:

Drug: PF-06801591

Drug: Bacillus Calmette-Guerin

BCG induction and maintenance

Active Comparator group

Description:

Bacillus Calmette Guerin (induction and maintenance).

Treatment:

Drug: Bacillus Calmette-Guerin

BCG Unresponsive CIS

Experimental group

Description:

PF-06801591

Treatment:

Drug: PF-06801591

BCG Unresponsive NMIBC

Experimental group

Description:

PF-06801591

Treatment:

Drug: PF-06801591