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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Bladder Cancer
• Intervention / Treatment: Drug: N-803 and BCG; Drug: N-803

• Study Type: Interventional
• Enrollment (Actual): 190
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Paula Bradshaw; Phone Number: 844-413-8500; Email: paula.bradshaw@immunitybio.com

Study Locations

• United States
  • Alaska
    • Anchorage, Alaska, United States, 99503
      • Alaska Clinical Research Center
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
      • Arkansas Urology
  • California
    • Los Angeles, California, United States, 90024
      • UCLA Department of Urology
    • Newport Beach, California, United States, 92663
      • Hoag Memorial Hospital
    • Sherman Oaks, California, United States, 91411
      • Skyline Urology
    • Torrance, California, United States, 90505
      • Skyline Urology
  • Colorado
    • Englewood, Colorado, United States, 80113
      • Urology Associates, PC
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami Miller School of Medicine-Sylvester Comprehensive Cancer Center
    • Pompano Beach, Florida, United States, 33060
      • Clinical Research Center of Florida
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • Georgia
    • Augusta, Georgia, United States, 30905
      • Dwight D. Eisenhower Army Medical Center
  • Hawaii
    • Honolulu, Hawaii, United States, 96814
      • University of Hawaii Cancer Center
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Adult & Pediatric Urology
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • Accument Rx
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Insitute
    • Garden City, New York, United States, 11530
      • Winthrop University Hospital Department of Urology
    • New York, New York, United States, 10016
      • Manhattan Medical Research
    • Poughkeepsie, New York, United States, 12601
      • Premier Medical Group of the Hudson Valley
    • Rochester, New York, United States, 14642
      • University of Rochester
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • UNC Chapel Hill
    • Raleigh, North Carolina, United States, 27612
      • Associated Urologists of North Carolina
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Virginia
    • Richmond, Virginia, United States, 23235
      • Virginia Urology
  • Washington
    • Tacoma, Washington, United States, 98431
      • Madigan Army Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Disease-Free Rate	Cohort B: Assess disease-free rate at 12 months since first study treatment	12 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response	Cohort A & Cohort C: Assess duration of complete response Cohort B: Assess disease-free survival	60 months
Response	Cohort A & Cohort C: Assess complete response rate at 6 months. Cohort B: Assess disease-free rate at 6 months	6 months
Response	Cohort A & Cohort C: Assess complete response rate at 9 months. Cohort B: Assess disease-free rate at 9 months	9 months
Response	Cohort A & Cohort C: Assess complete response rate at 12 months. Cohort B: Assess disease-free rate at 12 months	12 months
Response	Cohort A & Cohort C: Assess complete response rate at 18 months. Cohort B: Assess disease-free rate at 18 months	18 months
Response	Cohort A & Cohort C: Assess complete response rate at 24 months. Cohort B: Assess disease-free rate at 24 months	24 months
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

Collaborators and Investigators

• Sponsor: ImmunityBio, Inc.
• Investigators: Principal Investigator: Karim Chamie, MD, University of California, Los Angeles

Study record dates

Study Major Dates

• Study Start (Actual): June 2, 2017
• Primary Completion (Estimated): April 1, 2025
• Study Completion (Estimated): October 1, 2028

Study Registration Dates

• First Submitted: January 13, 2017
• First Submitted That Met QC Criteria: January 13, 2017
• First Posted (Estimated): January 18, 2017

Study Record Updates

• Last Update Posted (Actual): April 8, 2024
• Last Update Submitted That Met QC Criteria: April 5, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: immunotherapy; bladder cancer; NMIBC; BCG; interleukin-15; intravesical; non-muscle invasive
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Urinary Bladder Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urinary Bladder Neoplasms; Non-Muscle Invasive Bladder Neoplasms
• Other Study ID Numbers: CA-ALT-803-01-16

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No