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 Persistent or Recurrent Following BCG Induction (KEYNOTE-676)
- Conditions
- bladder cancerurothelial carcinoma10038364
- Registration Number
- NL-OMON55727
- Lead Sponsor
- Merck Sharp & Dohme (MSD)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 21
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, high-grade 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
OR
•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
OR
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 long term 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
17. Have adequate organ function. Specimens must be collected within 14 days
prior to randomization
18. 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 fr
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 non-resectable (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-PD L2
agent or with an agent directed to another stimulatory or co inhibitory 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 treatment
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 that required steroids or has
current pneumonitis
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
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 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 invasiveurothelial 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-PD L2
agent or with an agent directed to another stimulatory or co inhibitory T-cell
receptor
26. Has received any prior treatment with BCG for their NMIBC within the past 2
years prior to study entry
27. Has received prior systemic anti-cancer therapy including investigational
agents within 4 weeks of start of study treatment
28. Has received prior radiotherapy within 2 weeks of start of study trea
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Cohort A:<br /><br>Complete response among CIS participants<br /><br><br /><br>Cohort B:<br /><br>Event-free survival (EFS)</p><br>
- Secondary Outcome Measures
Name Time Method <p>Cohort A: EFS<br /><br><br /><br>Cohort B: None</p><br>