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

Sponsor

ImmunityBio, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT03022825

Collaborator

(none)

200

Enrollment

Locations

Arm

Anticipated Duration (Months)

6.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Bladder Cancer	Drug: N-803 and BCG Drug: N-803	Phase 2/Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

200 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jun 2, 2017

Anticipated Primary Completion Date :

Jan 1, 2023

Anticipated Study Completion Date :

Jan 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: BCG+N-803	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. 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.

Arm

Intervention/Treatment

Experimental: BCG+N-803

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.

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.

Outcome Measures

Primary Outcome Measures

Complete Response [60 Months]
Cohort A & Cohort C: Assess incidence of complete response of CIS (with or without Ta/T1 papillary disease) patients at any time
Disease-Free Rate [12 Months]
Cohort B: Assess disease-free rate at 12 months since first study treatment

Secondary Outcome Measures

Response [60 months]
Cohort A & Cohort C: Assess duration of complete response Cohort B: Assess disease-free survival
Response [6 months]
Cohort A & Cohort C: Assess complete response rate at 6 months. Cohort B: Assess disease-free rate at 6 months
Response [9 months]
Cohort A & Cohort C: Assess complete response rate at 9 months. Cohort B: Assess disease-free rate at 9 months
Response [12 months]
Cohort A & Cohort C: Assess complete response rate at 12 months. Cohort B: Assess disease-free rate at 12 months
Response [18 months]
Cohort A & Cohort C: Assess complete response rate at 18 months. Cohort B: Assess disease-free rate at 18 months
Response [24 months]
Cohort A & Cohort C: Assess complete response rate at 24 months. Cohort B: Assess disease-free rate at 24 months
Complete Response [60 months]
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)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Alaska Clinical Research Center	Anchorage	Alaska	United States	99503
2	Arkansas Urology	Little Rock	Arkansas	United States	72211
3	West Coast Urology	Inglewood	California	United States	90301
4	UCLA Department of Urology	Los Angeles	California	United States	90024
5	Hoag Memorial Hospital	Newport Beach	California	United States	92663
6	Skyline Urology	Sherman Oaks	California	United States	91411
7	Skyline Urology	Torrance	California	United States	90505
8	Urology Associates, PC	Englewood	Colorado	United States	80113
9	Eastern Connecticut Hematology and Oncology Associates	Norwich	Connecticut	United States	06360
10	University of Miami Miller School of Medicine-Sylvester Comprehensive Cancer Center	Miami	Florida	United States	33136
11	Clinical Research Center of Florida	Pompano Beach	Florida	United States	33060
12	Moffitt Cancer Center	Tampa	Florida	United States	33612
13	Dwight D. Eisenhower Army Medical Center	Augusta	Georgia	United States	30905
14	University of Hawaii Cancer Center	Honolulu	Hawaii	United States	96814
15	University of Chicago Medical Center	Chicago	Illinois	United States	60637
16	University of Michigan	Ann Arbor	Michigan	United States	48109
17	Karmanos Cancer Institute	Detroit	Michigan	United States	48201
18	Adult & Pediatric Urology	Omaha	Nebraska	United States	68114
19	Accument Rx	Albuquerque	New Mexico	United States	87109
20	Roswell Park Cancer Insitute	Buffalo	New York	United States	14263
21	Winthrop University Hospital Department of Urology	Garden City	New York	United States	11530
22	Manhattan Medical Research	New York	New York	United States	10016
23	Premier Medical Group of the Hudson Valley	Poughkeepsie	New York	United States	12601
24	University of Rochester	Rochester	New York	United States	14642
25	UNC Chapel Hill	Chapel Hill	North Carolina	United States	27599
26	Associated Urologists of North Carolina	Raleigh	North Carolina	United States	27612
27	Clinical Research Solutions	Middleburg Heights	Ohio	United States	44130
28	Toledo Clinic	Toledo	Ohio	United States	43606
29	Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107
30	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232
31	Virginia Urology	Richmond	Virginia	United States	23235
32	Madigan Army Medical Center	Tacoma	Washington	United States	98431