A Study Testing a New Drug (ALT-803) With BCG to Treat Early-Stage Bladder Cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Immunitybio Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

completed 5 Feb 2026

Decision date (initial)

2025-08-26

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

ImmunityBio, Inc

External identifiers

EU CT number

2025-521223-78-00

ClinicalTrials.gov

NCT02138734

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

Cohort A:
 To determine the efficacy of the combination of N-803 plus BCG
compared to BCG alone in patients with CIS disease (with or without
Ta/T1) in terms of complete response (CR) rate at 6 months using cystoscopy, confirmatory bladder biopsy (if required), and urine cytology;
Cohort B:
 To determine the efficacy of the combination of N-803 plus BCG compared to BCG alone in patients with high-grade papillary disease (Ta/T1 only) in terms of disease-free survival (DFS) using cystoscopy, confirmatory bladder biopsy (if required), and urine cytology.

Secondary objectives 1

1. Cohort A:  To assess the safety profile of patients treated with N-803 plus BCG compared to patients treated with BCG alone.  To assess the duration of complete response (CR) of patients treated with N-803 plus BCG compared to patients treated with BCG alone.  To assess the CR rate and duration of CR (all recurrent bladder cancer including low grade Ta disease) of patients treated with N-803 plus BCG compared to patients treated with BCG alone.  To assess progression free survival (PFS) for patients treated with N803 plus BCG compared to patients treated with BCG alone.  To assess the overall survival (OS) for patients treated with N-803 plus BCG compared to patients treated with BCG alone.  To assess the disease-specific survival (DSS) for patients treated with N-803 plus BCG compared to patients treated with BCG alone.  To assess the time to disease worsening for patients treated with N-803 plus BCG compared to patients treated with BCG alone.  To assess the cystectomy-free rate for patients treated with N-803 plus BCG compared to patients treated with BCG alone.  To assess the quality of life (QoL) of patients treated with N-803 plus BCG compared to patients treated with BCG alone.  To assess the long-term CR rate (as determined by the Investigator) following completion of QUILT-2.005 phase 2b. Cohort B:  To assess the safety profile of patients treated with N-803 plus BCG compared to patients treated with BCG alone.  To assess the DFS rate at 3, 9, 12, 18, 24, 30, and 36 months of patients treated with N-803 plus BCG compared to patients treated with BCG alone.  To assess the DFS (all recurrent bladder cancer, including low grade Ta disease) of patients treated with N-803 plus BCG compared to patients treated with BCG alone.  To assess PFS for patients treated with N-803 plus BCG compared to patients treated with BCG alone.  To assess the overall survival for patients treated with N-803 plus BCG compared to patients treated with BCG alone.  To assess the disease-specific survival (DSS) for patients treated with N-803 plus BCG compared to patients treated with BCG alone.  To assess the time to disease worsening for patients treated with N-803 plus BCG compared to patients treated with BCG alone.  To assess the cystectomy-free rate for patients treated with N-803 plus BCG compared to patients treated with BCG alone.  To assess the QoL of patients treated with N-803 plus BCG compared to patients treated with BCG alone.  To assess long-term DFS (as determined by the Investigator) since the randomization in QUILT-2.005 phase 2b. Cohorts A and B:  To obtain yearly long-term follow-up (LTFU) data from subjects who were treated in QUILT-2.005 phase 2b for a maximum of 10 years. Exploratory (Cohorts A and B):  To characterize the immunogenicity profile of N-803 in patients treated with N-803 plus BCG.  To characterize the pathologic whole slide images (WSI) from baseline and on-study biopsies and their correlation to treatment outcome.

Conditions and MedDRA coding

Non-Muscle Invasive Bladder Cancer

Study design 6 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. Patients must meet ALL of the following criteria for inclusion in the study: 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). a. Cohort A: Histologically confirmed CIS (with or without Ta/T1 disease); Cohort B: Histologically confirmed high-grade papillary disease (Ta/T1 only). b. Patients are eligible if the diagnostic biopsy was done within 3 months of treatment start and a cystoscopy demonstrating no resectable disease within 90 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. If a repeat biopsy is required for any reason, a negative result does not exclude the patient, provided bladder cancer was confirmed in the initial diagnosis. c. 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: a. Have not received prior intravesical BCG; or b. Previously received BCG, but stopped receiving more than 3 years before date of randomization. 6. Laboratory tests performed within 21 days of treatment start: a. Absolute lymphocyte count ≥ Institutional lower limit of normal b. Absolute neutrophil count (AGC/ANC) ≥ 1,000/µL c. Platelets ≥ 100,000/µL [Patients may be transfused to meet this requirement] d. Hemoglobin ≥ 8 g/dL [Patients may be transfused to meet this requirement] e. Calculated glomerular filtration rate (GFR*) >40 mL/min or Serum creatinine ≤ 1.5 x ULN f. Total bilirubin ≤ 2.0 X ULN g. AST, ALT, ALP ≤ 3.0 X ULN * 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 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 (eg, hysterectomy or tubal ligation) and males must agree to use barrier methods of birth control while on study. 10. Provide signed informed consent and agree to comply with all protocol-specified procedures and follow-up evaluations.

Exclusion criteria 1

1. Patients with ANY of the following criteria are excluded from participation in the study: 1. Prior BCG treatment in the last 3 years or known hypersensitivity to BCG or known history of BCG Unresponsive NMIBC. 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 FDAauthorized 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 (Appendix 16.4) 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 central nervous system (CNS) disease. 7. Active systemic infection requiring parenteral antibiotic therapy. All prior infections must have resolved following optimal therapy. 8. Concurrent febrile illness, active urinary tract infection, active tuberculosis, a history of hypotension or anaphylactic reaction to BCG or N-803. 9. Ongoing chronic systemic steroid therapy required (>10 mg oral prednisone daily or equivalent). 10. 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 (eg, 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. 11. Psychiatric illness/social situations that would limit compliance with study requirements. 12. Other illness that in the opinion of the Investigator would exclude the patient from participating in this study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Cohort A: Comparison of the CR rate at 6 months for patients treated with N-803 plus BCG versus patients treated with BCG alone. Cohort B: The estimate of the median DFS will be provided for each treatment group along with the 95% confidence interval. Cohort A and B: Due to the allocation of a small amount of alpha to the unplanned interim efficacy analyses, the final primary efficacy analyses will be conducted at alpha level of 0.0499.

Secondary endpoints 1

1. Cohort A 1. Duration of CR 2. CR rate at 3, 9, 12, 18, 24, 30, and 36 months Cohort B 1. DFS rate at 3, 9, 12, 18, 24, 30, and 36 months. Cohort A 1. CR rate at 3, 9, 12, 18, 24, 30, and 36 months (all recurrent bladder cancer including low grade Ta disease) 2. Duration of CR (all recurrent bladder cancer, including low grade Ta disease).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Immunitybio Inc.

Sponsor organisation

Immunitybio Inc.

Address

9920 Jefferson Boulevard

City

Culver City

Postcode

90232-3506

Country

United States

Scientific contact point

Organisation

Immunitybio Inc.

Contact name

ImmunityBio, Inc.

Public contact point

Organisation

Immunitybio Inc.

Contact name

Dr. Leander Grode

Third parties 1

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 20 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications