Brief Title: BCG in Combination With Durvalumab in Adult BCG-naïve, High-risk NMIBC Participants

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Incidence of Grade 3 or 4 Possibly related adverse events (PRAEs)

Primary Outcome 1 - Timeframe: From the date of the first dose of study treatment (Day 1) until 6 months after the initiation of study treatment

CONDITION

• Non-Muscle- Invasive Bladder Cancer

ELIGIBILITY

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

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

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