QUILT-3.032: A Multicenter Clinical Trial of Intravesical Bacillus Calmette-Guerin (BCG) in Combination With ALT-803 (N-803) in Patients With BCG Unresponsive High Grade Non-Muscle Invasive Bladder Cancer

NCT ID: NCT03022825

Last Updated: 2025-10-16

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 190 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-06-02
• Study Completion Date: 2029-03-01

Brief Summary

This is a Phase II/III, open-label, single-arm, multicenter study of intravesical BCG plus N-803 or N-803 only in patients with BCG unresponsive high grade non-muscle invasive bladder cancer (NMIBC). All patients treated in the study will receive via a urinary catheter in the bladder, BCG plus N-803 or N-803 only weekly for 6 consecutive weeks (initial induction treatment period). After the first disease assessment, eligible patients will receive either a 3-week maintenance course or a 6-week re-induction course (second treatment period) at Month 3. Eligible patients will continue to receive maintenance treatment in the third treatment period at Months 6, 9, 12, and 18. Eligible patients have the option to receive maintenance treatment in the fourth treatment period at Months 24, 30, and 36. The study duration is 60 months.

Conditions

Bladder Cancer

Study Design

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

Study Groups

BCG+N-803

Group Type: EXPERIMENTAL

N-803 and BCG

Intervention Type: DRUG

BCG and N-803 will be mixed together (with saline) and administered via intravesical instillation weekly for 6 consecutive weeks (induction). After the first disease assessment, eligible patients will receive either a 3-week maintenance course or a 6-week re-induction course (second treatment period) at Month 3. Eligible patients will continue to receive maintenance treatment in the third treatment period at Months 6, 9, 12, and 18. Eligible patients have the option to receive maintenance treatment in the fourth treatment period at Months 24, 30, and 36.

N-803

Intervention Type: DRUG

N-803 will be administered via intravesical instillation weekly for 6 consecutive weeks (induction). After the first disease assessment, eligible patients will receive either a 3-week maintenance course or a 6-week re-induction course (second treatment period) at Month 3. Eligible patients will continue to receive maintenance treatment in the third treatment period at Months 6, 9, 12, and 18. Eligible patients have the option to receive maintenance treatment in the fourth treatment period at Months 24, 30, and 36.

Interventions

N-803 and BCG

BCG and N-803 will be mixed together (with saline) and administered via intravesical instillation weekly for 6 consecutive weeks (induction). After the first disease assessment, eligible patients will receive either a 3-week maintenance course or a 6-week re-induction course (second treatment period) at Month 3. Eligible patients will continue to receive maintenance treatment in the third treatment period at Months 6, 9, 12, and 18. Eligible patients have the option to receive maintenance treatment in the fourth treatment period at Months 24, 30, and 36.

Intervention Type: DRUG

N-803

N-803 will be administered via intravesical instillation weekly for 6 consecutive weeks (induction). After the first disease assessment, eligible patients will receive either a 3-week maintenance course or a 6-week re-induction course (second treatment period) at Month 3. Eligible patients will continue to receive maintenance treatment in the third treatment period at Months 6, 9, 12, and 18. Eligible patients have the option to receive maintenance treatment in the fourth treatment period at Months 24, 30, and 36.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Male or female patients 18 years of age or older
• Histologic confirmation of non-muscle invasive bladder cancer of the transitional cell carcinoma high-grade subtype (mixed histology tumors allowed if transitional cell histology is predominant histology).
• Histologically confirmed presence of BCG-unresponsive CIS (with or without Ta or T1 disease) or histologically confirmed presence of BCG-unresponsive high-grade Ta or T1 disease.
• Absence of resectable disease after transurethral resection (TURBT) procedures (residual carcinoma in situ (CIS) acceptable; patients with T1 tumors must undergo repeat resection and biopsy [inclusive of muscularis propria] if initial biopsy did not include muscularis propria). Patients with high-grade Ta and/or T1 disease should have complete resection before study treatment.
• BCG-unresponsive disease as defined as: (a) Persistent or recurrent CIS (+/- recurrent Ta/T1 disease) within 12 months of receiving adequate BCG (at least five of six doses doses of an initial induction course plus either at least two of three doses of maintenance therapy or at least two of six doses of a second induction course); or (b) Recurrent high-grade Ta/T1 disease within 6 months of completion of adequate BCG (at least five of six doses of an initial induction course plus either at least two of three doses of maintenance therapy or at least two of six doses of a second induction course); or (c) T1 high-grade disease at the first evaluation following an induction BCG course alone (at least five of six doses of an initial induction course).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
• Voluntary written informed consent and HIPAA authorization and agree to comply with all protocol-specified procedures and follow-up evaluations

Exclusion Criteria

• Recurrence of BCG unresponsive Ta/T1 disease (without presence of CIS) > 6 months after last BCG instillation or BCG unresponsive CIS > 12 months after last BCG instillation.
• Life expectancy <2 years
• Any of the following clinical laboratory values at the time of enrollment: (1) Absolute neutrophil count (ANC) <800/µL or (2) Platelets < 50,000/µL
• Liver function abnormalities as indicated by ongoing hepatic enzyme elevation (AST or ALT) >2 times upper limit of normal (ULN)
• Renal insufficiency as indicated by a creatinine level >3 times ULN
• History of or evidence of muscle-invasive, locally advanced, metastatic and/or extravesical bladder cancer (inclusive of the prostatic urethra); or any other cancer within the past 5 years that is progressing or requires active treatment. Exceptions are adequately treated basal cell or squamous cell skin cancer that has undergone potentially curative therapy or in situ cervical cancer; and adequately treated stage I or II cancer or stable prostate cancer from which the patient is currently in complete remission, and is under active surveillance or hormone control.
• Symptomatic congestive heart failure (CHF), New York Heart Association (NYHA) Class III or IV heart failure or other clinical signs of severe cardiac dysfunction
• Severe/unstable angina pectoris, or myocardial infarction within 6 months prior to study entry
• History or evidence of uncontrollable central nervous system (CNS) disease
• Active systemic infection requiring parenteral antibiotic therapy. All prior infections must have resolved following optimal therapy
• Concurrent febrile illness, active urinary tract infection, active tuberculosis, a history of hypotension or anaphylactic reactions
• Ongoing chronic systemic steroid therapy required (>10 mg oral prednisone daily or equivalent)
• Women who are pregnant or nursing. Female patients of childbearing potential must have a negative pregnancy test and must adhere to using a medically acceptable method of birth control prior to screening and agree to continue its use during the study and for 30 days after the last dose of study drug, or be surgically sterilized (e.g., hysterectomy or tubal ligation). Women of childbearing potential are defined as any female who has experienced menarche and who is NOT permanently sterile or postmenopausal. Postmenopausal is defined as 12 consecutive months with no menses without an alternative medical cause. Males must agree to use barrier methods of birth control while on study and for 90 days post last dose of study drug.
• Patients currently receiving investigational or commercial anti-cancer agents or anti-cancer therapies other than BCG, ALT-803 and supportive care therapies for active disease.
• Concurrent use of other investigational agents (not including FDA authorized drugs for the prevention and treatment of COVID-19).
• Other illness or condition, including laboratory abnormalities, which in the opinion of the Investigator would exclude the patient from participating in this study. This includes, but is not limited to, serious medical conditions or psychiatric illness likely to interfere with participation in the study.

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

Sponsors

ImmunityBio, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Karim Chamie, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, Los Angeles

Locations

Alaska Clinical Research Center

Anchorage, Alaska, United States

Arkansas Urology

Little Rock, Arkansas, United States

UCLA Department of Urology

Los Angeles, California, United States

Hoag Memorial Hospital

Newport Beach, California, United States

Skyline Urology

Sherman Oaks, California, United States

Skyline Urology

Torrance, California, United States

Urology Associates, PC

Englewood, Colorado, United States

University of Miami Miller School of Medicine-Sylvester Comprehensive Cancer Center

Miami, Florida, United States

Clinical Research Center of Florida

Pompano Beach, Florida, United States

Moffitt Cancer Center

Tampa, Florida, United States

Dwight D. Eisenhower Army Medical Center

Augusta, Georgia, United States

University of Hawaii Cancer Center

Honolulu, Hawaii, United States

University of Chicago Medical Center

Chicago, Illinois, United States

University of Michigan

Ann Arbor, Michigan, United States

Karmanos Cancer Institute

Detroit, Michigan, United States

Adult & Pediatric Urology

Omaha, Nebraska, United States

Accument Rx

Albuquerque, New Mexico, United States

Roswell Park Cancer Insitute

Buffalo, New York, United States

Winthrop University Hospital Department of Urology

Garden City, New York, United States

Integrated Medical Professionals

New York, New York, United States

Premier Medical Group of the Hudson Valley

Poughkeepsie, New York, United States

University of Rochester

Rochester, New York, United States

UNC Chapel Hill

Chapel Hill, North Carolina, United States

Associated Urologists of North Carolina

Raleigh, North Carolina, United States

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Virginia Urology

Richmond, Virginia, United States

Madigan Army Medical Center

Tacoma, Washington, United States

Countries

United States

References

Chamie K, Chang SS, Rosser CJ, Kramolowski E, Gonzalgo ML, Sexton WJ, Spilman P, Sender L, Reddy S, Soon-Shiong P. N-803 Plus BCG Treatment for BCG-Naive or -Unresponsive Non-Muscle Invasive Bladder Cancer: A Plain Language Review. Future Oncol. 2024;20(31):2307-2317. doi: 10.1080/14796694.2024.2363744. Epub 2024 Jul 2.

Reference Type: DERIVED

PMID: 38953850 (View on PubMed)

Other Identifiers

CA-ALT-803-01-16

Identifier Type: -

Identifier Source: org_study_id