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
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- Pfizer
- 入组人数
- 1,068
- 试验地点
- 178
- 主要终点
- Event free survival (Cohort A: Arm A compared to Arm C)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
PF-06801591 + BCG induction and maintenance
PF-06801591 in combination with Bacillus Calmette Guerin(induction+maintenance).
干预措施: PF-06801591 (Drug)
PF-06801591 + BCG induction and maintenance
PF-06801591 in combination with Bacillus Calmette Guerin(induction+maintenance).
干预措施: Bacillus Calmette-Guerin (Drug)
PF-06801591 + BCG induction only
PF-06801591 in combination with Bacillus Calmette Guerin (induction only).
干预措施: PF-06801591 (Drug)
PF-06801591 + BCG induction only
PF-06801591 in combination with Bacillus Calmette Guerin (induction only).
干预措施: Bacillus Calmette-Guerin (Drug)
BCG induction and maintenance
Bacillus Calmette Guerin (induction and maintenance).
干预措施: Bacillus Calmette-Guerin (Drug)
BCG Unresponsive CIS
PF-06801591
干预措施: PF-06801591 (Drug)
BCG Unresponsive NMIBC
PF-06801591
干预措施: PF-06801591 (Drug)
结局指标
主要结局
Event free survival (Cohort A: Arm A compared to Arm C)
时间窗: 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) (Obsolete after stopping enrollment in Cohort B)
时间窗: 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) (Obsolete after stopping enrollment in Cohort B)
时间窗: 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.
次要结局
- Duration of CR for participants with CIS at randomization (Obsolete for Cohort B after stopping enrollment)(Randomization/registration up to 60 months from last participant randomized)
- Time to recurrence of low grade disease (Cohort A: Arm A, B, C)(Randomization up to 60 months from last participant randomized)
- Event free survival (Cohort A: Arm B compared to Arm C)(55 months after first participant randomized)
- Overall Survival (Cohort A: Arm A compared to Arm C)(Randomization up to 60 months from last participant randomized)
- Overall Survival (Cohort A: Arm B compared to Arm C)(Randomization up to 60 months from last participant randomized)
- Complete response rate in participants with CIS at randomization (Cohort A: Arm A, B, C)(Randomization up to 60 months from last participant randomized)
- Disease-specific survival (Cohort A: Arm A, B, C)(Randomization up to 60 months from last participant randomized)
- 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)(Randomization up to 60 months from last participant randomized)
- ctrough of PF-06801591 when in combination with BCG (induction and maintenance or induction). Cohort A: Arms A and B only.(Randomization up to 24 months)
- Incidence of ADA/Nab of PF-06801591 when in combination with BCG (induction and maintenance or induction). Cohort A: Arms A and B only.(Randomization up to 24 months)
- Tumor sample biomarker status based on PD-L1 expression (high or low) (Obsolete for Cohort B after stopping enrollment)(Baseline)
- Time to cystectomy (Obsolete for Cohort B after stopping enrollment)(Randomization/registration to date of cystectomy (up to 5 years after last participant is randomized))
- Health-related quality of life as measured by PTAB (Patient Treatment Administration Burden Questionnaire) (Obsolete for Cohort B after stopping enrollment)(Randomization/registration up to 24 months)
- 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)(Baseline up to 60 months from the last participant randomized)
- Percentage of Participants With Laboratory Abnormalities (Obsolete for Cohort B after stopping enrollment)(Baseline up to 60 months from last participant randomized)
- 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)(Randomization/registration up to 60 months from the last participant randomized)
- Complete response rate at 12 months (Cohort B1) (Obsolete after stopping enrollment in Cohort B)(12 months after last participant's initial assessment)
- Event Free Survival (Cohort B1) (Obsolete after stopping enrollment in Cohort B)(Registration to 5 years after last participant randomized.)
- Overall Survival (Cohorts B1 and B2) (Obsolete after stopping enrollment in Cohort B)(Registration to 5 years after last participant randomized.)
- ctrough of PF-06801591 (Cohorts B1 and B2) (Obsolete after stopping enrollment in Cohort B)(Registration up to 24 months)
- Incidence of ADA/Nab of PF-06801591 (Cohorts B1 and B2) (Obsolete after stopping enrollment in Cohort B)(Registration up to 24 months)
- cmax of PF-06801591 (Cohort B2 only) (Obsolete after stopping enrollment in Cohort B)(Registration up to 24 months)