2022-501817-29-00招募中3 期
A Phase 3, Randomized, Comparator-controlled Clinical Trial to Study the Efficacy and Safety of Pembrolizumab (MK-3475) in combination with Bacillus Calmette-Guerin (BCG) in Participants with High-risk Non-muscle Invasive Bladder Cancer (HR NMIBC) that is either Persistent or Recurrent Following BCG Induction or that is Naïve to BCG Treatment (KEYNOTE-676)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 559
- 试验地点
- 57
- 主要终点
- Complete Response Rate (CRR) by Blinded Independent Central Review (BICR) (Cohort A)
研究概览
简要总结
- Cohort A: To compare the CRR for the combination of pembrolizumab + BCG versus BCG alone in participants with CIS
- Cohort B: To compare the EFS between participants who receive pembrolizumab + BCG (reduced maintenance) versus BCG alone
- Cohort B: To compare the EFS between participants who receive pembrolizumab+ BCG (full maintenance) versus BCG alone
研究设计
- 分配方式
- Randomized
- 主要目的
- Unblinded open-label treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 是
入选标准
- •Have locally and blinded independent central review (BICR)-confirmed histological diagnosis of high-risk non-muscle invasive (T1, high grade Ta and/or CIS) UC of the bladder
- •Has undergone cystoscopy/ transurethral resection of bladder tumor (TURBT) to remove all resectable disease
- •Has provided tissue for biomarker analysis
- •Has Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
- •Has adequate organ function
- •During the treatment period and for ≥7 days after the last dose of BCG, male participants are EITHER abstinent from heterosexual intercourse as their preferred and usual lifestyle and agree to remain abstinent, OR, must agree to use contraception unless confirmed to be azoospermic
- •Female participants who are not pregnant, not breastfeeding, and either not a woman of child bearing potential (WOCBP); or are a WOCBP who agrees to use a contraception method that is highly effective or remains abstinent from heterosexual intercourse during the treatment period and for ≥7 days after the last dose of BCG or 120 days after the last dose of pembrolizumab, whichever comes last
- •BCG Post-induction Cohort (Cohort A) Only: Has been treated with one adequate course of BCG induction therapy for the treatment of HR NMIBC
- •BCG Post-induction Cohort (Cohort A) Only: Following adequate BCG induction therapy, must have persistent or recurrent HR NMIBC
排除标准
- •Has a history of or concurrent locally advanced (i.e., T2, T3, T4) or metastatic UC
- •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
- •Has an active infection or diagnosis requiring systemic antimicrobial therapy
- •Has a known history of human immunodeficiency virus (HIV) infection
- •Has a known history of Hepatitis B or known active Hepatitis C virus infection
- •Has current active tuberculosis
- •Has had an allogenic-tissue/solid organ transplant
- •Has any contraindication(s) to IV contrast or is otherwise unable to have screening imaging with IV contrast performed
- •BCG Post-induction Cohort (Cohort A) Only: Has persistent T1 disease following an induction course of BCG
- •BCG Naïve Cohort (Cohort B) Only: Has received any prior treatment with BCG for their NMIBC within the past 2 years prior to study entry
- •Has concurrent extra-vesical (i.e, urethra, ureter, renal pelvis) non-muscle invasive urothelial carcinoma or a history of extra-vesical non-muscle invasive UC
- •Has received prior therapy with 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
- •Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks of start of study treatment
- •Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks of start of study treatment
- •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
- •Has a known additional malignancy that is progressing or requires active treatment within the past 3 years
- •Has an active autoimmune disease that has required systemic treatment in past 2 years
- •Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
结局指标
主要结局
Complete Response Rate (CRR) by Blinded Independent Central Review (BICR) (Cohort A)
Complete Response Rate (CRR) by Blinded Independent Central Review (BICR) (Cohort A)
Event-Free Survival (EFS) (Cohort B)
Event-Free Survival (EFS) (Cohort B)
次要结局
- EFS (Cohort A)
- Recurrence-Free Survival (RFS) (Cohorts A and B)
- Overall Survival (OS) (Cohorts A and B)
- Disease Specific Survival (DSS) (Cohorts A and B)
- Time to Cystectomy (Cohorts A and B)
- 12-Month EFS Rate (Cohort A)
- Duration of Response (DOR) (Cohorts A and B)
- 12-Month DOR Rate (Cohorts A and B)
- Percentage of Participants Experiencing Adverse Events (AEs) (Cohorts A and B)
- Percentage of Participants Discontinuing Study Drug Due to AEs (Cohorts A and B)
- Change from Baseline in the European Organization for Research and Treatment of Cancer (EORTC)-Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status/Quality of Life (Items 29 and 30) Combined Score (Cohorts A and B)
- Change from Baseline in EORTC-QLQ-C30 Physical Functioning (Items 1-5) Combined Score (Cohorts A and B)
- Change from Baseline in EORTC-QLQ-Non-muscle Invasive Bladder Cancer Module 24 (NMIBC24) Total Score (Cohorts A and B)
- Change from Baseline in European Quality of Life (EuroQoL)-5 Dimensions, 5-level Questionnaire (EQ-5D-5L) Visual Analogue Score (VAS) (Cohorts A and B)
- Time to Deterioration (TTD) in the EORTC-QLQ-C30 Global Health Status/Quality of Life (Items 29 and 30) Combined Score (Cohorts A and B)
- TTD in the EQ-5D-5L VAS (Cohorts A and B)
- CRR by BICR (Cohort B)
- 24-Month EFS Rate (Cohort B)
研究者
Hema Dave
Scientific
Merck Sharp & Dohme LLC
研究点 (57)
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