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) - A Phase 3 trial of BCG with or without pembrolizumab (MK-3475) for HR NMIBC (KEYNOTE-676)

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.0 个研究点目标入组 1,405 人开始时间: 2018年9月14日最近更新: 2021年11月29日

适应症

试验速览

阶段: 1 期
状态: 进行中（未招募）
发起方: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
入组人数: 1,405

研究概览入排标准研究者记录与标识符相似试验

研究概览

简要总结

暂无简介。

研究设计

研究类型: Interventional clinical trial of medicinal product

入排标准

性别: All

入选标准

•Cohort A-BCG Post-induction Cohort
•1. Male/female participants who are at least 18 years of age on the day
•of providing documented informed consent will be enrolled in this study
•2. Have locally and BICR-confirmed histological diagnosis of high-risk non-muscle
•invasive (T1, highgrade Ta and/or CIS) UC of the bladder
•3. Have been treated with one adequate course of BCG induction therapy
•for the treatment of HR NMIBC defined as at least 5 intravesical
•instillations of BCG within a 10-week period of time
•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. Specimens must be collected within 14
•days prior to randomization
•9. Male participants are eligible to participate if they agree to the
•following during the treatment period and for at least 7 days after the
•last dose of BCG:
•Be abstinent from heterosexual intercourse as their preferred and usual
•lifestyle (abstinent on a long-term and persistent basis) and agree to
•remain abstinent
•Must agree to use contraception unless confirmed to be azoospermic
•(vasectomized or secondary to medical cause)
•10. A female participant is eligible to participate if she is not pregnant or
•breastfeeding, and at least 1 of the following conditions applies:
•a) Is not a WOCBP
•b) Is a WOCBP and using a contraceptive method that is highly effective
•(with a failure rate of <1% per year), or be abstinent from heterosexual
•intercourse as their preferred and usual lifestyle (abstinent on a longterm
•and persistent basis), during the treatment period and for at least 7
•days after the last dose of BCG or 120 days after the last dose of
•pembrolizumab, whichever comes last
•11. The participant (or legally acceptable representative) provides
•documented informed consent/assent for the study. The participant may
•also provide consent/assent for FBR. However, the participant may
•participate in the main study without participating in FBR
•Cohort B-BCG Naïve Cohort
•12. Male/female participants who are at least 18 years of age on the day
•of providing documented informed consent will be enrolled in this study
•13. Have locally and BICR-confirmed histological diagnosis of high-risk non-muscle
•invasive (T1, highgrade Ta and/or CIS) UC of the bladder
•14. Have undergone cystoscopy/TURBT to remove all resectable disease
•within 12 weeks prior to randomization
•15. Have provided tissue for biomarker analysis from the most recent
•TURBT/biopsy procedures from which tumor sample is available
•16. Have a performance status of 0, 1 or 2 on the ECOG performance
•Scale, as assessed within 14 days prior to randomization
另有 9 项未显示

排除标准

•Cohort A-BCG Post-induction Cohort
•1. Has persistent (remains present or occurs 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 a history of or concurrent locally advanced (ie, T2,
•T3, T4) or metastatic UC
•3. Has concurrent extra-vesical non-muscle invasive urothelial
•carcinoma, concurrent upper tract involvement, or invasive prostatic UC
•including T1 or greater disease, or ductal invasion
•4. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PDL2
•agent or with an agent directed to another stimulatory or coinhibitory
•T-cell receptor
•5. Has received prior systemic anti-cancer therapy including
•investigational agents within 4 weeks of start of study treatment
•6. Has received prior radiotherapy within 2 weeks of start of study
•7. Has received a live vaccine within 30 days of start of study treatment
•8. 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
•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 hypersensitivity to pembrolizumab and/or any of its excipients
•12. Has an active autoimmune disease that has required systemic
•treatment in past 2 years
•13. Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
•14. Has 1 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
•15. Has an active infection or diagnosis requiring systemic antimicrobial therapy
•16. Has a known history of HIV infection
•17. Has a known history of Hepatitis B or known active Hepatitis C virus infection
•18. Has current active tuberculosis
•19. Has known psychiatric or substance abuse disorder that would
•interfere with cooperating with the requirements of the study
•20. Has had an allogenic-tissue/solid organ transplant
•21. Has any contraindication(s) to IV contrast or is otherwise unable to
•have screening imaging with IV contrast performed
•Cohort B-BCG Naïve Cohort
•22. Has a history of or concurrent locally advanced or metastatic UC
•23.Has concurrent extra-vesical non-muscle invasive UC or a history of extra-vesical non-muscle invasive UC that recurred within 2 years prior.
•24. Has any contraindication(s) to IV contrast or is otherwise unable to have screening imaging with IV contrast performed
•25. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PDL2
•agent or with an agent directed to another stimulatory or coinhibitory
•T-cell receptor
•26. Has received any prior treatment with BCG for their NMIBC within
•the past 2 years prior to study entry
另有 5 项未显示

研究者

发起方

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

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