N-803 + BCG for Bladder Cancer

Recruiting at 29 trial locations

Overseen By Andrew Trainer, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: ImmunityBio, Inc.

Must be taking: BCG

Must not be taking: Systemic steroids

Disqualifiers: Life expectancy <2 years, Liver abnormalities, Renal insufficiency, Severe cardiac dysfunction, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

190 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new treatments for individuals with a type of bladder cancer that hasn't responded to standard BCG therapy (Bacillus Calmette-Guérin). Researchers are examining the effectiveness of BCG combined with a drug called N-803 (an IL-15 superagonist complex), or N-803 alone, in treating this resistant cancer. Participants will receive treatment directly into the bladder over several weeks and months. This trial may suit those with high-grade bladder cancer that hasn't improved with BCG treatment. As a Phase 2 trial, it focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important research.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of N-803 and BCG for bladder cancer is generally easy for patients to handle. In studies, most people experienced only mild side effects, while serious side effects were rare, as the treatments had "modest toxic effects." N-803 offers a good balance of benefits to risks, meaning the advantages of the treatment outweigh the possible downsides.

The studies also found that in patients whose bladder cancer did not respond to standard BCG treatment, the survival rate related to bladder cancer was very high at 99% over two years. This suggests the treatment is not only safe but also potentially effective in managing the disease.

Overall, the evidence so far indicates that N-803 and BCG are safe options for treating this type of bladder cancer, with most patients handling the treatment well. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of N-803 with BCG for bladder cancer because it offers a novel approach to enhancing the immune response against cancer cells. While the standard treatment, BCG, works by stimulating the body's immune system to attack bladder cancer cells, N-803 acts as an immune cytokine that boosts this response even further. This synergy between BCG and N-803 has the potential to improve treatment efficacy by enhancing the body's natural defenses, potentially leading to better outcomes for patients with bladder cancer.

What evidence suggests that this trial's treatments could be effective for bladder cancer?

This trial will evaluate the combination of N-803 with BCG for treating high-grade non-muscle invasive bladder cancer (NMIBC), particularly when standard BCG treatment has been ineffective. Research has shown that this combination may help treat NMIBC. In a study with 160 patients, this combination resulted in a 99% bladder cancer-specific survival rate over two years. Specifically, 71% of patients with carcinoma in situ (CIS) experienced positive outcomes. Another study found that patients remained disease-free for an average of 19.3 months. These results suggest that using N-803 with BCG could be a promising treatment option for this type of bladder cancer. ^{1 2 6 7 8}

Who Is on the Research Team?

Karim Chamie, MD

Principal Investigator

University of California, Los Angeles

Are You a Good Fit for This Trial?

Adults over 18 with high-grade non-muscle invasive bladder cancer unresponsive to BCG treatment can join. They must have had specific prior treatments, no resectable disease after surgery, and an ECOG status of 0-2. Exclusions include life expectancy under 2 years, certain heart conditions, active infections or recent severe infections, ongoing steroid therapy above a set dose, other cancer treatments or investigational drugs (excluding COVID-19), serious medical or psychiatric issues that could affect participation.

Inclusion Criteria

My bladder cancer cannot be removed by surgery, but I've had all necessary resections.

I can take care of myself and am up and about more than half of my waking hours.

Voluntary written informed consent and HIPAA authorization and agree to comply with all protocol-specified procedures and follow-up evaluations

Exclusion Criteria

Your blood test results show low levels of white blood cells or platelets.

My liver enzymes are more than twice the normal limit.

I do not have uncontrollable brain or nervous system disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Initial Induction Treatment

Participants receive BCG plus N-803 or N-803 only weekly for 6 consecutive weeks

6 weeks

Second Treatment Period

Eligible patients receive either a 3-week maintenance course or a 6-week re-induction course at Month 3

3-6 weeks

Third Treatment Period

Eligible patients continue to receive maintenance treatment at Months 6, 9, 12, and 18

12 months

Fourth Treatment Period (Optional)

Eligible patients have the option to receive maintenance treatment at Months 24, 30, and 36

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

What Are the Treatments Tested in This Trial?

Interventions

• BCG
• N-803

Trial Overview The trial is testing the effectiveness of intravesical BCG combined with N-803 versus N-803 alone in treating bladder cancer that hasn't responded to previous BCG therapy. Patients receive these treatments through a urinary catheter for six weeks initially and may continue maintenance treatment at various intervals up to three years if eligible.

How Is the Trial Designed?

Group I: BCG+N-803 Experimental Treatment 2 Interventions

BCG is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Bacillus Calmette-Guérin for:

• Non-muscle invasive bladder cancer

Approved in European Union as Bacillus Calmette-Guérin for:

• Non-muscle invasive bladder cancer

Approved in Canada as Bacillus Calmette-Guérin for:

• Non-muscle invasive bladder cancer

Who Is Running the Clinical Trial?

ImmunityBio, Inc.

Lead Sponsor

Trials

75

Recruited

5,000+

Richard Adcock

ImmunityBio, Inc.

Chief Executive Officer since 2024

Information not available

Dr. Patrick Soon-Shiong

ImmunityBio, Inc.

Chief Medical Officer since 2021

MD

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8096327/

Safety, Tolerability, and Long-Term Clinical Outcomes of an IL ... This phase 1b trial found the combination of intravesical N-803 and BCG to be associated with modest toxic effects, low immunogenicity, and substantial ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.4508

Final clinical results of pivotal trial of IL-15RαFc ... Conclusions: In 160 patients with BCG-unresponsive NMIBC, there is a 99% bladder cancer specific overall survival at 2 years. In CIS patients 71 ...

3. cancernetwork.com cancernetwork.com/view/intravesical-bcg-plus-novel-il-15-superagonist-complex-improves-dfs-in-bcg-unresponsive-non-muscle-invasive-bladder-cancer

Intravesical BCG Plus Novel IL-15 Superagonist Complex ... Patients with Bacillus Calmette-Guerin–unresponsive non-muscle invasive bladder cancer experienced a disease-free survival benefit when ...

4. auajournals.org auajournals.org/doi/10.1097/UPJ.0000000000000517

Quality of Life in the Phase 2/3 Trial of N-803 Plus Bacillus ... In cohort B, the median disease-free survival was 19.3 months. The efficacy findings for QUILT-3.032 demonstrate N-803 plus BCG's ability to ...

5. immunitybio.com immunitybio.com/immunitybio-announces-fda-approval-of-anktiva-first-in-class-il-15-receptor-agonist-for-bcg-unresponsive-non-muscle-invasive-bladder-cancer/

ANKTIVA FDA Approval: First-in-Class IL-15 Agonist for ... FDA approves ImmunityBio's ANKTIVA, a groundbreaking IL-15 receptor agonist for BCG-unresponsive non-muscle invasive bladder cancer (NMIBC).

6. immunitybio.com immunitybio.com/nejm-evidence-publishes-results-for-immunitybios-quilt-3-032-registrational-trial-of-il-15-superagonist-n-803-plus-bcg-in-patients-with-bladder-cancer/

NEJM Evidence Publishes Results for ImmunityBio's QUILT ... NEJM Evidence has published results from the QUILT 3.032 trial studying N-803 plus BCG in adults with NMIBC CIS with or without Ta/T1 papillary disease.

7. asco.org asco.org/abstracts-presentations/ABSTRACT325995

Phase II/III clinical results of IL-15RαFc superagonist N-803 ... N-803 represents a novel treatment option for BCG unresponsive CIS with a favorable benefit:risk ratio, in a therapeutically challenging disease.

8. jhoonline.biomedcentral.com jhoonline.biomedcentral.com/articles/10.1186/s13045-025-01664-8

IL-15: from discovery to FDA approval In data reported by the FDA, 62% of the 77 patients enrolled had a complete response, with 58% of patients sustaining this complete response for ...