A Phase III, 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
Study Identifier:
B011006
CT.gov Identifier:
EudraCT Identifier:
EU Trial (CTIS) Number:
Study Contact Information:
N/A
Study Complete
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Study Summary
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)
To demonstrate that PF-06801591 + BCG (induction and maintenance) is superior to BCG (induction and maintenance) in prolonging event-free survival (EFS) in participants with high-risk NMIBC.
Assessments:
Efficacy is assessed by cystoscopy and urine cytology every 12 wk for 2 y and every 24 wk thereafter and by biopsy and imaging as clinically indicated.
To learn about the safety and effects of the study medicine (sasanlimab) in people with non-muscle invasive bladder cancer.
To estimate the CR rate of PF-06801591 alone in participants with BCG unresponsive CIS
To evaluate the EFS of PF-06801591 alone in participants with BCG unresponsive NMIBC.
To evaluate sasanlimab administered subcutaneously in patients with BCG-unresponsive NMIBC.
To report PRO data not previously presented from CREST for Arms A and C assessing the impact of sasanlimab with BCG on QOL.
Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
Phase
The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
III
Sex
Female & Male
Age
18+ years
Study Drug
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Study Status
Indicates the current recruitment status or the expanded access status
Study Complete
Requirements information
Inclusion criteria
- All Cohorts
- Age
- Participant must be >or=18 years of age, at the time of signing the informed consent (except in Japan, where participants must be >or=20 years).
- Type of Participant and Disease Characteristics
- 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) defined as any of the following per World Health Organization grading system:
- a.T1 tumor;
- b.High-grade Ta tumor;
- c.Carcinoma in situ (CIS);
- 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 for participants in Cohort A, or within 12 weeks prior to initiation of study intervention for participants in Cohorts B1 and B2. A second TURBT must have been
- performed if indicated according to the current locally applicable guidelines, ie, American Urological Association, European Association of Urology.
- Availability of the tumor tissue from the most recent TURBT for the assessment of the PD-L1 expression. If a second TURBT was performed,
- as indicated according to the current locally applicable guidelines, the
- tumor tissue from the TURBT procedure that supports the primary diagnosis for study eligibility should be the tumor tissue used for the PDL1 expression testing.
- ECOG Performance Status (PS)
- Adequate Bone Marrow Function (without hematopoietic growth factor or transfusion support within 14 days prior to study randomization for participants in Cohort A, or within 14 days prior to initiation of study intervention for participants in Cohorts B1 and B2 ), including:
- a. Absolute neutrophil count (ANC) >or=1,500/mm3 or >or=1.5 x 109/L;
- b. Platelets >or=100,000/mm3 or 100 x 109/L;
- c. Hemoglobin >or=9 g/dL (>or=5.6 mmol/L).
- Adequate renal function defined by an estimated creatinine clearance >or=30 mL/min according to the Cockcroft Gault formula or by 24-hour urine collection for creatinine clearance, or according to local institutional standard method.
- Adequate liver function, including:
- a. Total serum bilirubin =1.5 × the upper limit of normal range (ULN). Participants with Gilbert syndrome who should have total serum bilirubin <3 x ULN;
- b. Aspartate and alanine aminotransferase (AST and ALT)
- Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other procedures.
- Sex
- Male or Female
- Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
- Informed Consent
- Capable of giving signed informed consent as described in Section 10.1.3 which includes compliance with the requirements and restrictions listed in the informed consent document (ICD) and in this protocol
- Cohorts B1 and B2 only
- Histological confirmed diagnosis of BCG-unresponsive high-risk, nonmuscle invasive TCC of the urothelium of the urinary bladder defined as any of the following:
- a) Cohort B1: persistent or recurrent CIS alone or with concomitant recurrent Ta/T1 disease within 12 months of completion of adequate BCG therapy. Stage and grade must be confirmed by the BICR prior to registration;
- b) Cohort B2: recurrent high-grade Ta/T1 disease within 6 months of completion of adequate BCG therapy;
- c) Cohort B2: T1 high-grade disease at the first evaluation following an adequate (at least 5 of 6 doses) induction BCG course.
- Have received adequate BCG therapy defined as at least one of the following:
- a) At least 5 of 6 doses of an initial induction course plus at least 2 of 3 doses of maintenance therapy;
- b) At least 5 of 6 doses of an initial induction course plus at least 2 of 6 doses of a second induction course.
- Note: The 2 courses described in "a" and "b" should have been administered within a 12 months period (ie the second course started within 12 months from the start of the first course).
- Note: Additional doses or courses of BCG above the minimum 5 + 2 described in "a" and "b" are allowed, and these do not have to be within the 12 month period.
- Note: The BCG dose administered in maintenance courses may be 1/2 or 1/3 dose in the event of a BCG shortage, according to NCCN and AUA treatment guidelines.
- Note: Prior BCG courses must have been comprised ONLY of one or more of the following strains: TICE, RIVM, TOKYO172, IMURON-VAC or Verity BCG (BCG-1), D2PB302, Danish (SSI).
- Have refused or are ineligible for radical cystectomy.
- Cohort B is a non-randomized, multicenter, multinational, open-label, phase 3 study and will enroll 160 patients with histologically confirmed BCG-unresponsive, high-risk, non-muscle invasive transitional cell carcinoma of the bladder urothelium (high-grade Ta or T1 tumor, or carcinoma in situ [CIS]) in 2 separate Cohorts, B1 and B2 (110 and 50 patients, respectively). Cohort B1 will enroll patients with persistent or recurrent CIS with or without concomitant recurrent high-grade Ta/T1 disease, within 12 months of completing adequate BCG therapy. Cohort B2 will enroll patients with recurrent high-grade Ta/T1 disease within 6 months of completing adequate BCG therapy.
Exclusion criteria
- Medical Conditions
- 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.
- Prior/Concomitant Therapy
- 7. Intravesical BCG therapy within 2 years prior to randomization. Prior intravesical chemotherapy for NMIBC is allowed.
- 8. Prior immunotherapy with anti PD-1, anti PD-L1, anti PD-L2, or anti cytotoxic Tlymphocyte-
- associated antigen-4 (CTLA-4) antibody.
- 9. Prior treatment with immunostimulatory agents including interleukin (IL)-2, IL-15, interferon (INF)-gamma.
- 10. Prior radiation therapy to the bladder.
- 11. Treatment with systemic anti-cancer therapy including investigational agents within 4 weeks prior to randomization.
- 12. Vaccination within 4 weeks from randomization and while on study treatment is prohibited except for administration of inactivated vaccines.
- 13. Patients with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids, and adrenal replacement doses >10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
- Prior/Concurrent Clinical Study Experience
- 14. Participation in other studies involving investigational drug(s) within 4 weeks prior to randomization.
- Diagnostic assessments
- 15. Known or documented absolute and/or relative contraindication of adjuvant intravesical BCG treatment:
- a. Prior BCG sepsis or systemic infection (including current urinary tract infection)
- b. Total bladder incontinence defined as use more than 6 pads in 24 hours
- c. Adverse experience to previous BCG instillation that resulted in treatment discontinuation or precludes re-treatment.
- 16. Clinically significant (ie, active) cardiovascular disease including the following: cerebral vascular accident/stroke (<6 months prior to randomization); myocardial infarction (<6 months prior to randomization); unstable angina; congestive heart failure ( >or=New York Heart Association Classification Class II); or serious cardiac arrhythmia (uncontrolled, clinically significant) requiring medication.
- 17. Q-T interval corrected for heart rate (QTc) >450 msec for male participants or QTc >470 msec for female participants or QTc >480 msec in participants with right bundle branch block
- Underwent major surgery within 2 weeks before randomization.
- 19Previous organ transplantation or allogeneic stem cell transplantation.
- 20The following medical history is known: immune-mediated colitis, inflammatory bowel disease, non-infectious pneumonia, or pulmonary fibrosis.
- 21The patient had an AE due to cancer treatment received >4 weeks ago and did not recover to a CTCAE level < or = 1 (except for hair loss and AEs judged by the investigator to not constitute a safety risk).
- 22Patients who are intolerant to antibodies or infused therapeutic proteins or have severe (grade > or = 3) allergic or immediate allergic reactions.
- 23Pregnant female patients; breastfeeding female patients; have reproductive potential but are unwilling or unable to use the high-efficiency prescribed in this research protocol during the entire study period and at least 6 months after the last use of PF-06801591 (only groups A and B) Contraceptive methods for male and female patients.
- 24Severe acute or chronic medical or psychiatric conditions, including recent (past year) or active suicidal ideation or behavior or laboratory abnormalities, may increase the risk associated with participating in research or the administration of research drugs, or may interfere with research results Explain that such patients are not suitable for entry into this study by the investigator.
- 25Patients are research center staff and their family members who are directly involved in the implementation of the research, research center staff who are otherwise supervised by the researcher, or Pfizer employees (including their family members) who are directly involved in the implementation of the research.
Clinical Study Information for Healthcare Providers
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Study Locations
Location
Investigator
Status
Condition(s) Treated at Site
Location
START Carolinas
Myrtle Beach, SC, United States, 29572
Investigator
Neal Shore
Status
Recruitment Complete
Condition(s) Treated at Site
Bladder