Efficacy and Safety of Pembrolizumab (MK-3475) in Combina... | NCT03711032

NCT03711032

ID	Type	Description
MK-3475-676	Other Identifier	MSD
194713	Other Identifier	JAPIC-CTI
jRCT2031200390	Registry Identifier	jRCT
2022-501817-29-00	Registry Identifier	EU CT
U1111-1282-1555	Registry Identifier	UTN
2018-001967-22	EudraCT Number

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
BCG plus Pembrolizumab: Post-induction Cohort A (Arm A-1)	Experimental	Participants receive BCG (Induction and Maintenance) in combination with 200 mg pembrolizumab administered intravenously (IV) every 3 weeks (Q3W) for 35 doses (~2 years).	Biological: Pembrolizumab Biological: BCG
BCG Monotherapy: Post-induction Cohort A (Arm A-2)	Experimental	Participants receive BCG monotherapy (Induction and Maintenance).	Biological: BCG
BCG plus Pembrolizumab: BCG Naïve Cohort B-Reduced Maintenance (Arm B-1)	Experimental	Participants receive BCG (Induction and reduced Maintenance) in combination with 400 mg pembrolizumab administered IV every 6 weeks (Q6W) for 9 doses (~1 year).	Biological: Pembrolizumab Biological: BCG
BCG plus Pembrolizumab: BCG Naïve Cohort B-Full Maintenance (Arm B-2)	Experimental	Participants receive BCG (Induction and full Maintenance) in combination with 400 mg pembrolizumab administered IV Q6W for 9 doses (~1 year).	Biological: Pembrolizumab Biological: BCG
BCG Monotherapy: BCG Naïve Cohort B (Arm B-3)	Experimental

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Pembrolizumab	Biological	Pembrolizumab IV infusion of 200 mg Q3W for BCG Post-Induction Cohort (Cohort A), or IV infusion of 400 mg Q6W for BCG Naïve Cohort (Cohort B), according to randomization

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Complete Response Rate (CRR) by Blinded Independent Central Review (BICR) (Cohort A)	CRR is defined as the percentage of participants with carcinoma in situ (CIS) achieving a complete response (CR).	Up to ~3.5 years
Event-Free Survival (EFS) (Cohort B)	EFS is defined as the time from randomization until urothelial carcinoma (UC)-defined event, or death due to any cause.	Up to ~5 years

Secondary Outcomes

Measure	Description	Time Frame
EFS (Cohort A)	EFS is defined as the time from randomization until UC-defined event, or death due to any cause.	Up to ~5 years
Recurrence-Free Survival (RFS) (Cohorts A and B)	RFS is defined as the time from randomization until the first occurrence of any UC recurrence, progression, or death due to any cause.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

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
Following adequate BCG induction therapy, must have persistent or recurrent HR NMIBC

Exclusion Criteria:

Has a history of or concurrent locally advanced (i.e., T2, T3, T4) or metastatic UC
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
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

ID	Term
C582435	pembrolizumab
D001500	BCG Vaccine

ID	Term
D032581	Tuberculosis Vaccines
D001428	Bacterial Vaccines
D014612	Vaccines
D001688	Biological Products
D045424	Complex Mixtures