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

NCT ID: NCT05943106

Last Updated: 2025-12-15

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-08-11
• Study Completion Date: 2027-03-31

Brief Summary

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.

Detailed Description

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).

Conditions

Non-Muscle- Invasive Bladder Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Durvalumab + BCG

Participants will receive Durvalumab for 13 cycles every 4 weeks (q4w) for a maximum 12 months. All participants will receive BCG (supplied by the site) intravesically, as induction weekly for 6 weeks. Patients will subsequently receive BCG for maintenance for 3 weekly doses at 3,6,12,18, and up to 24 months, at the physician's discretion.

Group Type: EXPERIMENTAL

Durvalumab

Intervention Type: BIOLOGICAL

Participants will receive Durvalumab via intravenous infusion from Week 1 for 13 cycles every 4 weeks (q4w) for maximum 12 months.

BCG

Intervention Type: BIOLOGICAL

Participants will receive BCG via intravesical as induction weekly for 6 weeks starting at Week 1, Day 1 and subsequently for maintenance for 3 weekly doses up to 3, 6, 12, 18, and 24 months, at the physician's discretion as Standard of care.

Interventions

Durvalumab

Participants will receive Durvalumab via intravenous infusion from Week 1 for 13 cycles every 4 weeks (q4w) for maximum 12 months.

Intervention Type: BIOLOGICAL

BCG

Participants will receive BCG via intravesical as induction weekly for 6 weeks starting at Week 1, Day 1 and subsequently for maintenance for 3 weekly doses up to 3, 6, 12, 18, and 24 months, at the physician's discretion as Standard of care.

Intervention Type: BIOLOGICAL

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 130 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Parexel

INDUSTRY

Sponsor Role: collaborator

AstraZeneca

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Research Site

Phoenix, Arizona, United States

Research Site

Little Rock, Arkansas, United States

Research Site

San Diego, California, United States

Research Site

Lakewood, Colorado, United States

Research Site

Hialeah, Florida, United States

Research Site

Jacksonville, Florida, United States

Research Site

Greenwood, Indiana, United States

Research Site

Wichita, Kansas, United States

Research Site

Baltimore, Maryland, United States

Research Site

Hanover, Maryland, United States

Research Site

Royal Oak, Michigan, United States

Research Site

Troy, Michigan, United States

Research Site

Syracuse, New York, United States

Research Site

Cincinnati, Ohio, United States

Research Site

Bala-Cynwyd, Pennsylvania, United States

Research Site

Myrtle Beach, South Carolina, United States

Research Site

Nashville, Tennessee, United States

Research Site

Austin, Texas, United States

Research Site

Spokane, Washington, United States

Countries

United States

Other Identifiers

D419JC00002

Identifier Type: -

Identifier Source: org_study_id