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

NCT05943106 | Active Not Recruiting Phase 3 FDA Drug

• 1 other identifier: D419JC00002
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 19

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.

Conditions

Non-Muscle- Invasive Bladder Cancer

Keywords

Bacillus Calmette-Guerin (BCG); BCG-naïve; immunotherapeutics; human mAb; Durvalumab; non-muscle-invasive bladder cancer (NMIBC)

Outcome Measures

Primary Outcomes (1)

• Incidence of Grade 3 or 4 Possibly related adverse events (PRAEs)

  A PRAE is defined as an AE that has been assessed by the Investigator to be possibly related to study treatment. A PRAE will be included if it has onset or worsens (by Investigator report of an increase in CTCAE (common terminology criteria for adverse events) grade relative to pre-treatment) within 6 months of initiation of study intervention and it has CTCAE Grade 3 or 4 recorded within this timeframe.

  From the date of the first dose of study treatment (Day 1) until 6 months after the initiation of study treatment

Secondary Outcomes (7)

• Number of participants with adverse events (AEs)

  From screening (Day -28 to -1) until 90 days following discontinuation of the last dose of study treatment (approximately 28 months)

• Percentage of patient-reported treatment tolerability symptoms assessed using specific PRO-CTCAE (Patient-Reported Outcomes- Common Terminology Criteria for Adverse Events)

  Up to 24 months

• Complete response rate (CRR)

  At 6 months

• Disease-free survival (DFS)

  At 12 months and 24 months

• Overall survival (OS)

  At 24 months

Study Arms (1)

Durvalumab + BCG

EXPERIMENTAL

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.

Biological: Durvalumab; Biological: BCG

Interventions

Durvalumab BIOLOGICAL

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

Durvalumab + BCG

BCG 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.

Durvalumab + BCG

Eligibility Criteria

• Age: 18 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead
• Parexel: collaborator

Study Sites (19)

Research Site

Phoenix, Arizona, 85054, United States

Location

Research Site

Little Rock, Arkansas, 72211, United States

Location

Research Site

San Diego, California, 92123, United States

Location

Research Site

Lakewood, Colorado, 80228, United States

Location

Research Site

Hialeah, Florida, 33016, United States

Location

Research Site

Jacksonville, Florida, 32209, United States

Location

Research Site

Greenwood, Indiana, 46143, United States

Location

Research Site

Wichita, Kansas, 67226, United States

Location

Research Site

Baltimore, Maryland, 21203, United States

Location

Research Site

Hanover, Maryland, 21076, United States

Location

Research Site

Royal Oak, Michigan, 48073, United States

Location

Research Site

Troy, Michigan, 48084, United States

Location

Research Site

Syracuse, New York, 13210, United States

Location

Research Site

Cincinnati, Ohio, 45212, United States

Location

Research Site

Bala-Cynwyd, Pennsylvania, 19004-1017, United States

Location

Research Site

Myrtle Beach, South Carolina, 29572, United States

Location

Research Site

Nashville, Tennessee, 37209, United States

Location

Research Site

Austin, Texas, 78759, United States

Location

Research Site

Spokane, Washington, 99202, United States

Location

MeSH Terms

Conditions

Non-Muscle Invasive Bladder Neoplasms

Interventions

durvalumab

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urinary Bladder Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 5, 2023
• First Posted: July 13, 2023
• Study Start: August 11, 2023
• Primary Completion: June 16, 2025
• Study Completion (Estimated): March 31, 2027
• Last Updated: March 11, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Locations

US (19)