A PHASE 3 TRIAL OF BCG WITH OR WITHOUT PEMBROLIZUMAB (MK-3475) FOR HR NMIBC (KEYNOTE-676)
- Conditions
- -D090 BladderBladderD090
- Registration Number
- PER-045-18
- Lead Sponsor
- Merck Sharp & Dohme Corp., una subsidiaria de Mer·ck & Co. Inc.,
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 0
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.
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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <br>Outcome name:Comparison of the pembrolizumab + BCG arm to the BCG arm using the stratified Miettinen and Nurminen method with strata weighting by sample size.<br>Measure:Complete Response (CR) in Carcinoma In Situ patients.<br>Timepoints:At full enrollment + 12 weeks or after 304 EFS events are accrued<br>
- Secondary Outcome Measures
Name Time Method