JXR UROL BALA PATAPSCO

The purpose of this study is to assess the safety, tolerability, and efficacy profile of durvalumab + BCG (induction and maintenance) combination therapy in adult United States participants with a histologically confirmed diagnosis of high-risk non-muscle-invasive bladder cancer (NMIBC), who have received no prior systemic therapy for NMIBC, and who are BCG-naïve.

This is an open-label, single-arm, multi-center, Phase IIIb US study exploring the combination of durvalumab and BCG (induction and maintenance) in participants with high-risk NMIBC.

Each participant will have screening activities up to 4 weeks before initiation of study intervention, receive study intervention for up to 24 months, followed by 3 months safety follow-up. Participants will continue to be followed up for survival until 2 years from the date of treatment initiation of the last participant enrolled in this study (approximately 42 months after first participant enrolled).

Inclusion Criteria:

• BCG-naïve (defined as participants not having received prior intravesical BCG or who previously received but stopped BCG more than 3 years before study entry).

• Local histological confirmation (based on cytology and/or pathology report) of high-risk transitional cell carcinoma of the urothelium of the urinary bladder confined to the mucosa or submucosa.

• Complete resection of all Ta/T1 papillary disease prior to enrollment, with the transurethral resection of bladder tumor (TURBT) removing high-risk NMIBC (non-muscle invasive bladder cancer) performed not more than 4 months before enrollment in the study.

• No prior radiotherapy for bladder cancer.

• A life expectancy of at least 12 weeks (90 days).

• Adequate organ and marrow function

• World Health Organization/Eastern Cooperative Oncology Group performance status of 0 or 1 at screening

• No prior exposure to immune-mediated therapy of cancer

• A candidate for BCG treatment.

• Local histological confirmation (based on cytology and/or pathology report) of high-risk transitional cell carcinoma of the urothelium of the urinary bladder confined to the mucosa or submucosa. A high-risk tumor is defined as one of the

Following: T1 tumor; High-grade/G3 tumor; Cis.

Exclusion Criteria:

• Evidence of muscle-invasive, locally advanced, metastatic, and/or extra-vesical bladder cancer (ie, T2, T3, T4, and / or Stage IV).

• Predominantly variant histology such as micropapillary, plasmacytoid, nested, sarcomatoid, microcystic, squamous and adeno variants of UC representing > 50% of tumor tissue or other than urothelial tumors as assessed by pathology.

• Evidence of lymphovascular invasion of bladder tumor, except if treatment with BCG is deemed to be the only clinically viable treatment.

• Immediate cystectomy is indicated.

• Known or documented absolute and/or relative contraindication of adjuvant intravesical BCG treatment.

• Concurrent extravesical, non-muscle-invasive transitional cell carcinoma of the urothelium.

• History of allogenic organ transplantation. Participants with any history of allogenic stem cell transplantation are also excluded.

• Active or prior documented autoimmune or inflammatory disorders.

• Participants with hypothyroidism stable on hormone replacement.

• History of active primary immunodeficiency.

• Active infection including hepatitis B (known positive HBV/HBsAg result), HCV, or HIV 1/2 (positive HIV) antibodies.

• Current or prior use of immunosuppressive medication within 14 days before the first durvalumab dose.

• Female participants who are pregnant or breastfeeding or male or female participants of reproductive potential who are not willing to employ highly effective birth control.

• Any concurrent chemotherapy, study intervention, biologic or hormonal therapy for cancer treatment; uncontrolled intercurrent illness;

• History of another primary malignancy except for Malignancy treated with curative intent and with no known active disease ≥ 2 years; Adequately treated nonmelanoma skin cancer or lentigo maligna without evidence of disease; Adequately treated CIS without evidence of disease; Prostate cancer of stage ≤ T2cN0M0 without biochemical recurrence or progression that in the opinion of the Investigator does not require active intervention.

• Previous or concurrent treatment with potent systemic immunostimulatory agents