A Study of Intravesical BCG in Combination With ALT-803 in Patients With Non-Muscle Invasive Bladder Cancer

A Study of Intravesical Bacillus Calmette-Guerin (BCG) in Combination With ALT-803 (N-803) in Patients With Non-Muscle Invasive Bladder Cancer

This is a Phase Ib/IIb, randomized, two-cohort, open-label, multicenter study of intravesical N-803 plus BCG versus BCG alone, in BCG naïve patients with high-grade NMIBC.

Study Overview

• Status: Active, not recruiting
• Conditions: Non-muscle Invasive Bladder Cancer
• Intervention / Treatment: Biological: BCG (50mg/instillation) + N-803 (400 μg/instillation); Biological: BCG (50mg/instillation)

Detailed Description

The study includes a dose escalation phase (phase Ib) and an expansion phase (phase IIb).

In the phase Ib, patients will be treated with intravesical N-803 in combination with BCG. The purpose of the phase Ib portion of the study is to evaluate the safety, identify the Maximum Tolerated Dose (MTD) of N-803 and determine the Recommended Dose (RD) level of N-803 in combination with BCG for the phase IIb expansion.

In the phase IIb expansion, patients will be randomized to receive either intravesical N-803 in combination with BCG or BCG alone. Patients will be enrolled into one of two study cohorts (Cohort A and Cohort B). These will be two independent study cohorts, evaluated separately for treatment efficacy.

• Study Type: Interventional
• Enrollment (Actual): 369
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• India
  • Ahmedabad, India
    • B J Medical College & Civil Hospital, Asarwa, Ahmedaba
  • Banjara Hills, India
    • Basavatarakam Indo American Cancer Hospital & Research Institute
  • Bengaluru, India, 560027
    • HCG Bangalore
  • Bikaner, India, 334003
    • SP Medical College and Hospital
  • Farīdkot, India, 151203
    • Guru Govnid Singh Medical College and Hospital
  • Gujrāt, India
    • Muljibhai Patel Urological Hospital
  • Kolkata, India
    • Chittaranjan National Cancer Institute
  • Kolkata, India, 700050
    • Binayak Multispecialty Hospital
  • Mysuru, India, 570001
    • KR Hospital
  • Nagar, India, 576104
    • KMC Manipal
  • Nagpur, India, 440012
    • Jasleen Hospital
  • Pune, India, 410506
    • Onco Life Cancer Center
  • Pune, India, 411040
    • Inamdar Hospital Pune
  • Rajkot, India
    • Urocare Hospital
  • Rajpura, India, 492099
    • All India Institute of Medical Sciences, Raipur
  • Uttar, India
    • Uttar Pradesh University of Medical Sciences
  • Visakhapatnam, India, 530040
    • HCG cancer Centre, Vizag
  • Visakhapatnam, India
    • Apollo Vizag
  • Andhra Pradesh
    • Visakhapatnam, Andhra Pradesh, India, 530040
      • HCG Cancer Centre
  • Chennai
    • Adyār, Chennai, India, 600036
      • Adyar cancer institute
  • Gujarat
    • Ahmedabad, Gujarat, India, 380060
      • HCG Aastha Cancer Centre
  • Maharashtra
    • Aurangabad, Maharashtra, India, 431001
      • Darakh Nursing Home and Kidney Stone Centre
    • Nagpur, Maharashtra, India, 440012
      • Kidney Centre Jasleen Hospital
    • Pune, Maharashtra, India, 412105
      • Indriyani Hospital & Cancer Institute
  • Nashik
    • Mumbai, Nashik, India, 422002
      • HCG Manavata Cancer Centre
  • National Capital Territory of Delhi
    • New Delhi, National Capital Territory of Delhi, India, 1100005
      • BLK-Max Super Specialty Hospital
  • Odisha
    • Bhubaneswar, Odisha, India, 751019
      • All India Institute of Medical Sciences,
  • Punjab
    • Amritsar, Punjab, India, 143501
      • Sri Guru Ram Das Institute of Medical Sciences and Research
  • Rajkort
    • Guntur, Rajkort, India, 360002
      • Urocare Hospital
  • Tamilnadu. India
    • Erode, Tamilnadu. India, India, 638012
      • Erode Cancer Centre
  • Telangana
    • Hyderabad, Telangana, India, 500032
      • Pi Health Cancer Hospital
  • Uttar
    • Agra, Uttar, India, 282002
      • Pushpanjali Hospital & Research Centre
  • Uttar Pardesh
    • Ghaziabad, Uttar Pardesh, India, 201012
      • Max Super Specialty Hospital
  • Varanasi
    • Sunderpur, Varanasi, India, 221005
      • Swami Harshankaranand JI Hospital and Research Centre
  • West Bengal
    • Kolkata, West Bengal, India, 700073
      • Govt. Medical College, Kolkata
• South Africa
  • Sandton, South Africa, 2191
    • Sunninghill Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • Alaska
    • Anchorage, Alaska, United States, 99503
      • Alaska Clinical Research Center
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic
    • Tucson, Arizona, United States, 85718
      • Center for Neurosciences
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
      • Arkansas Urology
  • California
    • Irvine, California, United States, 92618
      • Hoag Memorial Hospital Presbyterian
    • Los Angeles, California, United States, 90033
      • University of Southern California
    • Los Angeles, California, United States, 90095
      • UCLA Department of Urology
    • Orange, California, United States, 92868
      • University of California, Irvine Medical Center
    • Sacramento, California, United States, 95817
      • University of California, Davis
    • Sacramento, California, United States, 95823
      • Golden State Urology
    • San Diego, California, United States
      • University of California San Diego
    • Sherman Oaks, California, United States, 91411
      • Skyline Sherman Oaks
    • Torrance, California, United States, 90505
      • Skyline Urology
  • Connecticut
    • Norwich, Connecticut, United States, 06360
      • Eastern Connecticut Hematology & Oncology Associates
  • Florida
    • Hollywood, Florida, United States, 33021
      • Memorial Healthcare System
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic
    • Oxford, Florida, United States, 34484
      • Advanced Urology Institute
    • Pompano Beach, Florida, United States, 33060
      • Clinical Research Center Of Florida
    • Riverview, Florida, United States, 33578
      • Florida Urology Partners
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
    • Atlanta, Georgia, United States, 30328
      • Georgia Urology
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • University of Hawaii Cancer Center
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60612
      • Rush University
    • Chicago, Illinois, United States, 60415
      • Associated Urological Specialists
    • Glenview, Illinois, United States, 60026
      • UroPartners, LLC.
  • Indiana
    • Carmel, Indiana, United States, 46032
      • Urology Of Indiana
  • Kansas
    • Westwood, Kansas, United States, 66205
      • Kansas University Medical Center
    • Wichita, Kansas, United States, 67226
      • Wichita Urology
  • Kentucky
    • Lexington, Kentucky, United States, 40508
      • University of Kentucky Markey Cancer Center
  • Louisiana
    • Metairie, Louisiana, United States, 70002
      • Mary Bird Perkins Cancer Center
  • Maryland
    • Annapolis, Maryland, United States, 21401
      • Anne Arundel Urology
  • Massachusetts
    • Plymouth, Massachusetts, United States, 02360
      • Greater Boston Urology
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute
    • Royal Oak, Michigan, United States, 48703
      • Comprehensive Urology
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
    • Woodbury, Minnesota, United States, 55125
      • Minnesota Urology
  • Missouri
    • St Louis, Missouri, United States, 63141
      • Specialty Clinical Research of St. Louis
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Adult & Pediatric Urology
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth-Hitchcock Medical Center
  • New Jersey
    • Florham Park, New Jersey, United States, 07932
      • Summit Health
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • Urology Group of New Mexico (AccumetRx Clinical Research)
  • New York
    • Mineola, New York, United States, 11501
      • Winthrop University Hospital
    • New York, New York, United States, 10016
      • NYU Langone Health
    • New York, New York, United States, 10016
      • Integrated Medical Professionals
    • Poughkeepsie, New York, United States, 12601
      • Premier Medical Group of the Hudson Valley
    • Syracuse, New York, United States, 13210
      • Associated Medical Professionals of NY
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27278
      • University of North Carolina Chapel Hill
    • Raleigh, North Carolina, United States, 27612
      • Associated Urologists of North Carolina
  • Ohio
    • Centerville, Ohio, United States, 45459
      • Dayton Physicians Network
    • Cincinnati, Ohio, United States, 45212
      • The Urology Group
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati Cancer Center
    • Cleveland, Ohio, United States, 44195
      • The Cleveland Clinic Foundation
    • Gahanna, Ohio, United States, 43230
      • Central Ohio Urology Group
  • Pennsylvania
    • Bala-Cynwyd, Pennsylvania, United States, 19004
      • MidLantic urology
    • Philadelphia, Pennsylvania, United States, 19141
      • Thomas Jefferson University Hospital
  • South Carolina
    • North Charleston, South Carolina, United States, 29406
      • Lowcountry Urology Clinics
  • Tennessee
    • Chattanooga, Tennessee, United States, 37403
      • Erlanger Health
    • Nashville, Tennessee, United States, 37209
      • Urology Associates, PC
  • Texas
    • Arlington, Texas, United States, 76017
      • Urology Partners of North Texas
    • Austin, Texas, United States, 78705
      • Texas Oncology
    • Austin, Texas, United States, 78745
      • Urology Austin, PLLC
    • Houston, Texas, United States, 77027
      • Houston Metro Urology
    • San Antonio, Texas, United States, 78229
      • Urology San Antonio
  • Virginia
    • Alexandria, Virginia, United States, 22311
      • Potomac Urology
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University
    • Richmond, Virginia, United States, 23235
      • Virginia Urology
    • Virginia Beach, Virginia, United States, 23462
      • Urology of Virginia
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington School of Medicine
    • Spokane, Washington, United States, 99202
      • Spokane Urology

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria

1. 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).

   1. Cohort A: Histologically confirmed CIS (with or without Ta/T1 disease); Cohort B: Histologically confirmed high-grade papillary disease (Ta/T1 only).
   2. Patients are eligible if the diagnostic biopsy was done within 3 months of treatment start and a cystoscopy demonstrating no resectable disease was done within 6 calendar weeks (inclusive of 48 days) of treatment start (residual CIS is acceptable; patients with T1 disease must undergo repeat resection if muscularis propria is not present in each biopsy sample). Patients with high-grade Ta and/or T1 disease should have complete resection before study treatment.
   3. Upper tract imaging within 6 months prior to study entry must not be suspicious for upper tract malignancy.
2. Currently eligible for intravesical BCG therapy.
3. Age ≥ 18 years.
4. Performance status: ECOG performance status of 0, 1, or 2.

5. BCG-naive disease as defined as either of the following:

   1. Have not received prior intravesical BCG; or
   2. Previously received BCG, but stopped receiving more than 3 years before date of randomization.

6. Laboratory tests performed within 21 days of treatment start:

   1. Absolute lymphocyte count ≥ Institutional lower limit of normal
   2. Absolute neutrophil count (AGC/ANC) ≥ 1,000/μL
   3. Platelets ≥ 100,000/µL [Patients may be transfused to meet this requirement]
   4. Hemoglobin ≥ 8 g/dL [Patients may be transfused to meet this requirement]
   5. Calculated glomerular filtration rate (GFR*) >40 mL/min or Serum creatinine ≤ 1.5 x ULN
   6. Total bilirubin ≤ 2.0 X ULN
   7. AST, ALT, ALP ≤ 3.0 X ULN
7. Adequate pulmonary function without any clinical sign of severe pulmonary dysfunction. PFT > 50% FEV1 if clinically indicated by the investigator.
8. Negative serum pregnancy test if female and of childbearing potential (non-childbearing is defined as greater than one year postmenopausal or surgically sterilized).
9. Female participants of childbearing potential must adhere to using a medically accepted method of birth control prior to screening and agree to continue its use during the study or be surgically sterilized (e.g., hysterectomy or tubal ligation) and males must agree to use barrier methods of birth control while on study.

10. Provide signed informed consent and HIPPA authorization and agree to comply with all protocol-specified procedures and follow-up evaluations.

    • using the following Cockcroft-Gault equation to calculate the eGFR for this study: eGFR in mL/min = {(140-age in years) x (weight in kg) x F}/(serum creatinine in mg/dL x 72) Where F =1 if male; and 0.85 if female

Exclusion Criteria

1. Prior BCG treatment or known hypersensitivity to BCG. Patients who have received more than a single-dose post-operative treatment of mitomycin-C or gemcitabine following the most recent screening TURBT/biopsy are excluded.
2. Concurrent use of other investigational agents (not including FDA-authorized drugs for the prevention and treatment of COVID-19).
3. History of or evidence of muscle-invasive, locally advanced, metastatic and/or extravesical bladder cancer or any other cancer within the past 5 years, except: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage 1 or 2 cancer from which the patient is currently in complete remission, or stable prostate cancer (under active surveillance or hormone control).
4. Symptomatic congestive heart failure (CHF), NYHA (New York Heart Association) Class III or IV or other clinical signs of severe cardiac dysfunction.
5. Severe/unstable angina pectoris, or myocardial infarction within 6 months prior to study entry.
6. History or evidence of uncontrollable CNS disease.
7. Known HIV-positive.
8. Active systemic infection requiring parenteral antibiotic therapy. All prior infections must have resolved following optimal therapy.
9. Concurrent febrile illness, active urinary tract infection, active tuberculosis, a history of hypotension or anaphylactic reactions.
10. Ongoing chronic systemic steroid therapy required (>10 mg oral prednisone daily or equivalent).
11. 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.
12. Psychiatric illness/social situations that would limit compliance with study requirements.
13. Other illness that in the opinion of the investigator would exclude the patient from participating in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: N-803+BCG; (Phase Ib and IIb) for BCG-naive patients	Biological: BCG (50mg/instillation) + N-803 (400 μg/instillation); BCG and N-803 will be mixed together (with saline) and administered via intravesical instillation weekly for 6 consecutive weeks for induction. Phase IIb includes maintenance treatment consisting of BCG+N-803 for 3 consecutive weeks at 3, 6, 12, 18, 24, 30 and 36 months. An additional 6-week re-induction of BCG+N-803 for patients with eligible disease at 3 months in phase IIb is included.
Active Comparator: BCG alone; (Phase IIb) for BCG-naive patients	Biological: BCG (50mg/instillation); BCG will be administered via intravesical instillation weekly for 6 consecutive weeks for induction. Phase IIb includes maintenance treatment consisting of BCG for 3 consecutive weeks at 3, 6, 12, 18, 24, 30 and 36 months. An additional 6-week re-induction of BCG for patients with eligible disease at 3 months in phase IIb is included.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Response (CR) Rate	Patients in Cohort A: compare complete response rate between treatment arms using cystoscopy, confirmatory bladder biopsy and urine cytology.	6 Months
Disease Free Survival (DFS)	Patients in Cohort B: compare disease-free survival between treatment arms using cystoscopy, confirmatory bladder biopsy and urine cytology.	13 Years and 3 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	For phase IIb, Cohorts A & B: Time from randomization to disease progression or death.	13 Years and 3 Months
Disease specific survival	For phase IIb, Cohorts A & B: Time from randomization to death resulting from bladder cancer.	13 Years and 3 months
Time to disease worsening	For phase IIb, Cohorts A & B: Cystectomy or change in therapy indicative of more advanced disease, including systemic chemotherapy or radiation therapy.	13 Years and 3 Months
Cystectomy Free Rate	Cystectomy-free rate will be calculated for each treatment group as the ratio of the number of subjects who don't have documented cystectomy in the database divided by the number of subjects in the ITT (Intent to treat) population.	13 years and 3 months
Duration of Complete Response	To assess the duration of CR of patients treated with N-803 plus BCG compared to patients treated with BCG alone.	13 Years and 3 months
Complete Response Rate( All Recurrent Bladder Cancer Including Low Grade Ta Disease)	To assess the CR rate (all recurrent bladder cancer including low grade Ta disease) of patients treated with N-803 plus BCG compared to patients treated with BCG alone.	13 Years and 3 months
Cohort B: Disease Free Survival Rate	To assess DFS rate at 12, 18, 24, 30, and 36 months. The time from randomization until recurrence of high-grade Ta (excluding low grade Ta) or any grade T1, CIS, disease progression, cystectomy, change in therapy indicative of more advance disease or death (any cause), whichever occurs first.	36 Months
Cohort B: Disease Free Survival	DFS was assessed in the following groups: 1) All recurrent bladder cancer, including low grade Ta disease the time from randomization until recurrence of any grade Ta (including low grade Ta) or any grade T1, CIS, disease progression, cystectomy, change in therapy indicative of more advanced disease, or death (any cause), whichever occurs first 2) Patients who have high-grade Ta, low-grade T1, or CIS at 3-months and received re-induction, and have no evidence of > low-grade Ta disease at 6-months will be considered disease-free from randomization until a second recurrence > low-grade Ta 3) Patients who have high-grade Ta, low-grade T1, or CIS at 3-months and received re-induction, and have no evidence of any disease (including low grade Ta) at 6-months will be considered disease-free from randomization until a second recurrence ≥ low grade Ta.	13 Years and 3 Months
Vital signs and clinical laboratory assessment	Vital signs include heart rate, systolic and diastolic blood pressures, respiration rate, and body temperature. Labs include the following: complete blood count with differential, complete metabolic panel, and urinalysis.	36 Months
Safety Profile: Number and severity of treatment emergent AEs [Time Frame: 39 Months]	For phase Ib and phase IIb: Number of participants with TEAEs as assessed by CTCAE v4.03.	39 Months
Long Term Follow Up(LTFU) data from subjects who were treated	Yearly collection of LTFU data, which includes the following: survival status, bladder cancer status (high or low grade), cystoscopy results including number of cystoscopies done for each subject, biopsy results, upper tract evaluations, posttherapies and responses and outcomes of posttherapies, urine cytology results, and other medical history or treatments, if available, related to bladder cancer.	10 Years after treatment period visits
Overall survival	Time from randomization to death resulting from any cause to determine survival.	13 Years and 3 months
Long Term Complete Response Rate	To assess the long-term CR rate (as determined by the Investigator) following completion of QUILT-2.005 phase 2b.	13 years and 3 Months
Duration of Complete Response ( All Recurrent Bladder Cancer Including Low Grade Ta Disease)	Time from the date of first CR (All Recurrent bladder cancer including low grade Ta Disease) to the date of evidence that the subject no longer meets the definition for CR.	13 Years and 3 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory Endpoints- Immunogenicity: Serum level of anti-N-803 in patient samples	For phase Ib and IIb Measures the serum level of anti-N-803 in patient samples.	36 Months
Quality of Life Endpoint	Quality of Life (QoL) as assessed by the European Organization for Research and Treatment of Cancer (EORTC) questionnaires for patients with cancer (QLQ-C30) and for patients with NMIBC (QLQ-NMIBC24).	39 Months
Exploratory Endpoints- Whole Slide Images (Baseline and any on-study biopsy)	For Phase IIb	39 Months

Collaborators and Investigators

• Sponsor: ImmunityBio, Inc.
• Investigators: Study Director: Bobby Reddy, MD, ImmunityBio, Inc.

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): July 21, 2014
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): March 4, 2039

Study Registration Dates

• First Submitted: May 13, 2014
• First Submitted That Met QC Criteria: May 13, 2014
• First Posted (Estimated): May 15, 2014

Study Record Updates

• Last Update Posted (Actual): March 31, 2026
• Last Update Submitted That Met QC Criteria: March 26, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: immunotherapy; cancer; bladder cancer; antitumor; BCG; interleukin-15; transitional cell carcinoma; N-803; naive; instillation; intravesical; non-muscle invasive; ALT-803
• Additional Relevant MeSH Terms: Urogenital Diseases; Urogenital Neoplasms; Neoplasms by Site; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Urologic Neoplasms; Carcinoma; Urinary Bladder Diseases; Non-Muscle Invasive Bladder Neoplasms; Neoplasms; Urinary Bladder Neoplasms; Carcinoma, Transitional Cell; ALT-803
• Other Study ID Numbers: CA-ALT-803-01-14; QUILT-2.005

Drug and device information, study documents

• product manufactured in and exported from the U.S.: No