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

Bladder Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03022825
• Other study ID #: CA-ALT-803-01-16
• Status: Active, not recruiting
• Phase: Phase 2/Phase 3
• Start date: June 2, 2017
• Est. completion date: October 1, 2028

Study information

• Verified date: April 2024
• Source: ImmunityBio, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 190
• Est. completion date: October 1, 2028
• Est. primary completion date: April 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Bladder Cancer
• Urinary Bladder Neoplasms

Intervention

Drug:
• 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.
• 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.

Locations

Country	Name	City	State
United States	Accument Rx	Albuquerque	New Mexico
United States	Alaska Clinical Research Center	Anchorage	Alaska
United States	University of Michigan	Ann Arbor	Michigan
United States	Dwight D. Eisenhower Army Medical Center	Augusta	Georgia
United States	Roswell Park Cancer Insitute	Buffalo	New York
United States	UNC Chapel Hill	Chapel Hill	North Carolina
United States	University of Chicago Medical Center	Chicago	Illinois
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	Urology Associates, PC	Englewood	Colorado
United States	Winthrop University Hospital Department of Urology	Garden City	New York
United States	University of Hawaii Cancer Center	Honolulu	Hawaii
United States	Arkansas Urology	Little Rock	Arkansas
United States	UCLA Department of Urology	Los Angeles	California
United States	University of Miami Miller School of Medicine-Sylvester Comprehensive Cancer Center	Miami	Florida
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Manhattan Medical Research	New York	New York
United States	Hoag Memorial Hospital	Newport Beach	California
United States	Adult & Pediatric Urology	Omaha	Nebraska
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Clinical Research Center of Florida	Pompano Beach	Florida
United States	Premier Medical Group of the Hudson Valley	Poughkeepsie	New York
United States	Associated Urologists of North Carolina	Raleigh	North Carolina
United States	Virginia Urology	Richmond	Virginia
United States	University of Rochester	Rochester	New York
United States	Skyline Urology	Sherman Oaks	California
United States	Madigan Army Medical Center	Tacoma	Washington
United States	Moffitt Cancer Center	Tampa	Florida
United States	Skyline Urology	Torrance	California

Sponsors (1)

Lead Sponsor	Collaborator
ImmunityBio, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete Response	Cohort A & Cohort C: Assess incidence of complete response of CIS (with or without Ta/T1 papillary disease) patients at any time	60 Months
Primary	Disease-Free Rate	Cohort B: Assess disease-free rate at 12 months since first study treatment	12 Months
Secondary	Response	Cohort A & Cohort C: Assess duration of complete response Cohort B: Assess disease-free survival	60 months
Secondary	Response	Cohort A & Cohort C: Assess complete response rate at 6 months. Cohort B: Assess disease-free rate at 6 months	6 months
Secondary	Response	Cohort A & Cohort C: Assess complete response rate at 9 months. Cohort B: Assess disease-free rate at 9 months	9 months
Secondary	Response	Cohort A & Cohort C: Assess complete response rate at 12 months. Cohort B: Assess disease-free rate at 12 months	12 months
Secondary	Response	Cohort A & Cohort C: Assess complete response rate at 18 months. Cohort B: Assess disease-free rate at 18 months	18 months
Secondary	Response	Cohort A & Cohort C: Assess complete response rate at 24 months. Cohort B: Assess disease-free rate at 24 months	24 months
Secondary	Complete Response	Assess complete response rate at any time of CIS patients per central pathology review Duration of complete response (all recurrent bladder cancer, including low grade Ta disease)	60 months