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

• ClinicalTrials.gov Identifier: NCT03022825
• Recruitment Status: Active, not recruiting
• First Posted: January 18, 2017
• Last Update Posted: April 8, 2024
• Sponsor: ImmunityBio, Inc.
• Information provided by (Responsible Party): ImmunityBio, Inc.

Tracking Information

• First Submitted Date: January 13, 2017
• First Posted Date: January 18, 2017
• Last Update Posted Date: April 8, 2024
• Actual Study Start Date: June 2, 2017
• Estimated Primary Completion Date: April 1, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 3, 2021)

• Complete Response [ Time Frame: 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 [ Time Frame: 12 Months ]
  Cohort B: Assess disease-free rate at 12 months since first study treatment

• Original Primary Outcome Measures (submitted: January 13, 2017): Complete Response [ Time Frame: 6 months ]

Current Secondary Outcome Measures (submitted: November 3, 2021)

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

Original Secondary Outcome Measures (submitted: January 13, 2017)

• Complete Response [ Time Frame: 12 months ]
• Complete Response [ Time Frame: 18 months ]
• Complete Response [ Time Frame: 24 months ]
• Time to progression [ Time Frame: 24 months ]
• Overall Survival [ Time Frame: 24 months ]
• Time to cystectomy [ Time Frame: 24 months ]
• Incidence of adverse events [ Time Frame: 24 months ]
• Quality of Life (QOL) [ Time Frame: 24 months ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief 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
• 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2; Phase 3
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Bladder Cancer

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.
• 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.

Study Arms

Experimental: BCG+N-803

Interventions:

• Drug: N-803 and BCG
• Drug: N-803

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: April 18, 2023): 190
• Original Estimated Enrollment (submitted: January 13, 2017): 80
• Estimated Study Completion Date: October 1, 2028
• Estimated Primary Completion Date: April 1, 2025 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03022825
• Other Study ID Numbers: CA-ALT-803-01-16
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: ImmunityBio, Inc.
• Original Responsible Party: Altor BioScience
• Current Study Sponsor: ImmunityBio, Inc.
• Original Study Sponsor: Altor BioScience
• Collaborators: Not Provided

Investigators

• Principal Investigator: Karim Chamie, MD; University of California, Los Angeles

• PRS Account: ImmunityBio, Inc.
• Verification Date: April 2024