N-803 for Soft Tissue Cancer

Overseen By Study Coordinator

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Northwestern University

Must not be taking: IL-15 treatments, others

Disqualifiers: Uncontrolled hypertension, Active infection, Cardiovascular disease, Autoimmune disease, others

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

Compensation: Varies

Number of Visits: 2

Duration: Up to 104 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of a treatment called N-803 for individuals with certain types of soft tissue cancer, such as synovial sarcoma or myxoid/round cell liposarcoma. These rare cancers can return or worsen after initial therapy. N-803, a form of immunotherapy, helps the body's immune system combat cancer by activating immune cells. The trial seeks participants with these cancers who have previously received a specific type of cellular therapy but still experience growing or worsening cancer. Participants should be able to undergo a procedure to collect white blood cells and should have previously benefited from their initial therapy. As a Phase 1 trial, this research aims to understand how N-803 works in people, offering participants the chance to be among the first to receive this new treatment.

Is there any evidence suggesting that N-803 is likely to be safe for humans?

Research has shown that N-803, a type of immunotherapy, has generally been safe in earlier studies. In one study, N-803 combined with another treatment called BCG proved effective and well-tolerated by patients with a specific type of bladder cancer. This finding suggests that N-803 might also be safe for other cancers, such as synovial sarcoma or myxoid/round cell liposarcoma.

Another study found that N-803 caused only mild side effects, indicating that most people did not experience serious reactions. The treatment also exhibited low immunogenicity, meaning it did not trigger a strong immune response that could lead to complications.

Overall, early research suggests that N-803 is safe and tolerable. However, as this is an early phase study, further research is necessary to confirm these results for different types of cancer. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about N-803 for soft tissue cancer because it offers a novel approach to boosting the immune system. Unlike traditional chemotherapy and radiation, which directly target cancer cells, N-803 enhances the body's own immune response by stimulating natural killer (NK) cells. This unique mechanism of action could potentially lead to fewer side effects and a more targeted attack on cancer cells. Additionally, the subcutaneous delivery of N-803 allows for repeated dosages every two weeks, which may offer a more consistent therapeutic effect compared to standard treatments.

What evidence suggests that N-803 might be an effective treatment for soft tissue cancer?

Research has shown that N-803, which participants in this trial will receive, could be a promising treatment for soft tissue cancers like synovial sarcoma and myxoid/round cell liposarcoma. N-803 is a type of immunotherapy that uses a protein called interleukin-15 (IL-15) to strengthen the body's immune system to fight cancer cells. This treatment activates and increases immune cells, helping them attack cancer more effectively. Early studies suggest that N-803, when combined with other treatments, may benefit people with soft tissue sarcoma. While more research is needed, these initial findings offer encouragement for those considering N-803. ^{6 7 8 9 10}

Who Is on the Research Team?

Seth M Pollack, MD

Principal Investigator

Northwestern University

Are You a Good Fit for This Trial?

This trial is for patients with progressive synovial sarcoma or myxoid/round cell liposarcoma who have previously undergone adoptive cellular therapy using T-cell receptor therapy. Participants must have a type of soft tissue cancer that has not responded to prior treatments.

Inclusion Criteria

Patients must have measurable disease according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)

My cancer responded positively to the last treatment as shown by scans.

Absolute lymphocyte count (ALC) ≥ Institutional lower limit of normal (within screening window of 28 days up until pre-dose leukapheresis)

Exclusion Criteria

Patients who have received other IL-15 treatments since receiving TCR-T cells to the start of study treatment (C1D1)

Patients with high risk of bleeding, as determined by treating investigator

Patients who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to N-803 or history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive N-803 subcutaneously on day 1 of each cycle, with cycles repeating every 14 days for up to 52 cycles

Up to 104 weeks

Bi-weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• N-803

Trial Overview The trial is testing the safety and effectiveness of N-803, an immunotherapy drug, in treating specific types of soft tissue cancers. It involves procedures like biospecimen collection and various imaging tests (X-Ray, CT, MRI) to monitor effects.

How Is the Trial Designed?

Group I: Treatment (N-803, leukapheresis) Experimental Treatment 6 Interventions

Patients receive N-803 SC on day 1 of each cycle. Cycles repeat every 14 days for up to 52 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo leukapheresis during screening up until day 1 cycle 1 and during treatment on day 8 cycle 4. Patients also undergo CT, chest x-ray, or MRI as well as blood sample collection throughout the trial.

Who Is Running the Clinical Trial?

Northwestern University

Lead Sponsor

Trials

1,674

Recruited

989,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Citations

1. immunitybio.com immunitybio.com/immunitybio-announces-asco-genitourinary-cancer-symposium-presentation-of-phase-2-3-trial-for-bcg-unresponsive-non-muscle-invasive-bladder-cancer-cis-with-71-complete-response-rate/

ImmunityBio Announces ASCO Genitourinary Cancer ... N-803 has improved pharmacokinetic ... soft tissue sarcoma in combination with the company's synthetic immune modulator (Aldoxorubicin).

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8197753/

Phase 1 trial of N-803, an IL-15 receptor agonist, with ... N-803 is an IL-15 receptor superagonist complex, designed to optimize in vivo persistence and trans-presentation, thereby activating and expanding natural ...

3. jitc.bmj.com jitc.bmj.com/content/9/2/e001580

Immunotherapy for sarcomas: new frontiers and unveiled ... Herein, we discuss preclinical and clinical data highlighting how immunotherapy is being used in soft tissue sarcoma and bone sarcomas. Back to ...

4. mdpi.com mdpi.com/2227-9059/9/8/935

Novel Insights into the Immunotherapy of Soft Tissue ... In this review, we introduce the most important immune cell types infiltrating the STSs tumors and discuss different immunotherapies, as well as promising ...

5. umiamihealth.org umiamihealth.org/en/sylvester-comprehensive-cancer-center/impact-reports/2019/research-highlights/clinical-trial-explores-effectiveness-of-new-treatment-for-patients-with-bladder-cancer

Clinical Trial Explores Effectiveness of New Treatment for ... The Phase 2 trial examines whether the drug ALT-803, when added to the standard of care, the Bacillus Calmette-Guérin (BCG) vaccine, can enhance treatment ...

6. 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 ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT07085338

NCT07085338 | A Phase II Study With a Safety Run-In of ... Soft tissue lesions may be biopsied at any time point prior to enrollment. b. For MIBG non-avid tumors patient must have at least one FDG avid site and meet the ...

8. immunitybio.com immunitybio.com/immunitybio-announces-publication-of-preclinical-data-demonstrating-il-15-superagonist-n-803-improves-natural-killer-mediated-tumor-cell-killing/

ImmunityBio Announces Publication of Preclinical Data ... ImmunityBio Announces Publication of Preclinical Data Demonstrating IL-15 Superagonist N-803 Improves Natural Killer-Mediated Tumor Cell Killing.

9. onclive.com onclive.com/view/n-803-bcg-combo-shows-promising-responses-tolerability-in-bcg-unresponsive-bladder-cancer

N-803/BCG Combo Shows Promising Responses ... Bacille Calmette-Guérin (BCG) plus N-803 yielded promising responses and an encouraging safety profile in patients with BCG-unresponsive, non-muscle invasive ...

10. academic.oup.com academic.oup.com/oncolo/article/30/3/oyae267/7814737

Recurrent pancreatic cancer treated with N-803 and PD-L1 t ... Examples of N-803 efficacy in combination therapy include the achievement of durable complete responses in all patients in a phase 1b trial of N ...