D090 Bladder Bladder
Conditions
Interventions
None listed
Sponsors
Merck Sharp & Dohme LLC., (una subsidiaria de Merck & Co. Inc.)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male/female participants who are at least 18 years of age 2. Have histologically confirmed by BICR diagnosis of non-muscle invasive (T1, highgrade Ta and/or CIS) transitional cell carcinoma (TCC) of the bladder. 3. Have been treated with one adequate course of BCG induction therapy for the treatment of High-risk Non-muscle Invasive Bladder Cancer (HR NMIBC) 4. Following adequate BCG induction therapy, must have persistent or recurrent HR NMIBC 5.Have undergone cystoscopy/TURBT to remove all resectable disease within 12 weeks prior to randomization 6.Have provided tissue for biomarker analysis from the most recent TURBT/biopsy procedures from which tumor sample is available. 7.Have a performance status of 0, 1 or 2 on the ECOG Performance Scale, as assessed within 14 days prior to randomization. 8.Have adequate organ function within 14 days prior to randomization. 9. Participant is: - a female that is not pregnant, not breastfeeding, and is either not of childbearing potential (WOCBP) OR is a WOCBP who agrees to follow the contraceptive guidance per protocol during the treatment period and through 120 days after the last dose of study treatment or - a male that agrees to follow the contraceptive guidance per protocol during the treatment period and through 120 days after the last dose of study treatment 10.The participant (or legally acceptable representative if applicable) provides written informed consent for the study.
Exclusion criteria
Exclusion criteria: 1. Has persistent (remains present within 3 months (-2 weeks) to 6 months (+4 weeks) after start of BCG induction) T1 disease following an induction course of BCG. 2. Has muscle invasive (ie, T2, T3, T4), locally advanced non-resectable or metastatic urothelial carcinoma 3. Has concurrent extra-vesical (ie, urethra, ureter, renal pelvis) non-muscle invasive transitional cell carcinoma of the urothelium, concurrent upper tract involvement, or invasive prostatic TCC including T1 or greater disease, or ductal invasion. 4.A WOCBP who has a positive urine pregnancy test within 72 hours prior to randomization. 5.Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor 6.Has received prior systemic anti-cancer within 4 weeks of start of study treatment. 7.Has received prior radiotherapy within 2 weeks of start of study treatment.. 8.Has received a live vaccine within 30 days of start of study treatment. 9. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days of start of study treatment. 10. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years 11. Has an active autoimmune disease that has required systemic treatment in past 2 years 12. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis 13. Has one or more of the following contraindications to BCG: prior BCG sepsis or systemic infection, total bladder incontinence, or an adverse experience to a previous BCG instillation that resulted in treatment discontinuation and precludes retreating with BCG. 14. Has an active infection requiring systemic therapy (including a symptomatic UTI). 15. Has a known history of HIV infection, Hepatitis B or known active Hepatitis C virus or has evidence of active tuberculosis
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Comparison of the pembrolizumab + BCG arm to the BCG arm using the stratified Miettinen and Nurminen method with strata weighting by sample size. NAME OF THE RESULT: Complete Response (CR) in Carcinoma In Situ patients. PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: At full enrollment + 12 weeks or after 304 EFS events are accrued | — |
Secondary
| Measure | Time frame |
|---|---|
| Comparison of the pembrolizumab + BCG arm to the BCG arm using the stratified Miettinen and Nurminen method with strata weighting by sample size. NAME OF THE RESULT: Complete Response (CR) in Carcinoma In Situ patients. PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: At full enrollment + 12 weeks or after 304 EFS events are accrued;Kaplan-Meier method to estimate event rates within each treatment group. Stratified log-rank test to compare Pembrolizumab + BCG arm to the BCG arm. NAME OF THE RESULT: Event-free survival (EFS) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: At full enrollment + 12 weeks or after 304 EFS events are accrued;• Kaplan-Meier method to estimate event rates within each treatment group. Stratified log-rank test to compare Pembrolizumab + BCG arm to the BCG arm. • Non-parametric Kaplan-Meier method to estimate the survival curves. Stratified log-rank test to assess the treatment difference. • Non-parametric Kaplan-Meier method to estimate the survival curves. Stratified log-rank test to assess the treatment difference. • Non-parametric Kaplan-Meier method to estimate the survival curves. Stratified log-rank test to assess the treatment difference • Kaplan-Meier method to evaluate summary statistics. NAME OF THE RESULT: • Recurrence-free survival (RFS) • Overall survival (OS) • Disease-specific Survival (DSS) • Time to cystectomy • Duration of Response (DOR) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: At full enrollment + 12 weeks or after 304 EFS events are accrued;• probability of maintaining EFS at 12 months. • probability of maintaining DOR at 12 months starting from the time of CR. NAME OF THE RESULT: • 12-month EFS rate • 12-month DOR rate PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: 12 months after randomizat | — |
Countries
Australia, Austria, Belgium, Canada, Finland, Germany, Greece, Italy, Korea South, Malasya, Netherlands, Norway, Poland, Portugal, Spain, Turkey, United Kindgdom, United States
Outcome results
None listed