N-803 in Patients With Progressive Synovial Sarcoma and Myxoid/Round Cell Liposarcoma Previously Treated With Adoptive Cellular Therapy

NCT07261657 | Recruiting Early Phase 1 DMC FDA Drug

• 4 other identifiers: NU 25S06NCI-2025-08495STU00224911P30CA060553
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

This early phase I trial tests the safety and how well N-803 works in treating patients with synovial sarcoma (SS) or myxoid/round cell liposarcoma (MRCL) that is growing, spreading, or getting worse (progressive) after being treated with adoptive cellular therapy (ACT) using T-cell receptor therapy (T-CRT). Synovial sarcoma is a rare, slow-growing cancer that affects the soft tissues, like muscles or ligaments near the joints. Myxoid/round cell liposarcoma is a rare type of soft tissue sarcoma cancer that originates from fat cells usually in the arms and legs. N-803 is a type of immunotherapy-a treatment that helps patients' own immune system fight cancer, and it is made up of a natural protein called interleukin-15 (IL-15) that is important for growing and activating immune cells. Studies have shown that patients can progress after initially responding to TCR-T, so this trial will use N-803 to stimulate rare persisting cells (cells that survive treatment and cause treatment failure and disease relapse) to make them work better at attacking the cancer. Adoptive cell therapy is a type of therapy that uses a patient's own immune cells to fight cancer. T-cell receptor therapy is a type of ACT that can recognize better recognize and bind to protein in cancer cells. Giving N-803 may be safe and tolerable in patients with SS or MRCL.

Conditions

Synovial Sarcoma; Myxoid Liposarcoma; Round Cell Liposarcoma

Outcome Measures

Primary Outcomes (2)

• The expansion of rare persisting transferred T-cell receptor therapy

  Will be assessed using T-cell receptor sequencing or flow cytometry.

  Before and after eight weeks of N-803 therapy

• Incidence of adverse events

  Will be determined by the incidence, severity, and attribution of adverse events graded per National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.

  Up to 30 days after the last administration of N-803

Secondary Outcomes (3)

• Overall response rate

  Up to 4 years

• Six-month progression-free survival (PFS)

  Up to 4 years

• Median PFS

  Up to 4 years

Study Arms (1)

Treatment (N-803, leukapheresis)

EXPERIMENTAL

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.

Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Leukapheresis; Procedure: Magnetic Resonance Imaging; Biological: Nogapendekin Alfa Inbakicept; Procedure: X-Ray Imaging

Interventions

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Treatment (N-803, leukapheresis)

Leukapheresis PROCEDURE

Undergo leukapheresis

Also known as: Leukocyte Adsorptive Apheresis, Leukocytopheresis, Therapeutic Leukopheresis, White Blood Cell Reduction Apheresis

Treatment (N-803, leukapheresis)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Treatment (N-803, leukapheresis)

Nogapendekin Alfa Inbakicept BIOLOGICAL

Given SC

Also known as: ALT 803, ALT-803, ALT803, Anktiva, Fusion Protein Consisting of IL-15N72D and IL-15RASU/FC, IL-15N72D-IL-15RaSU/Fc, IL-15N72D/IL-15Ra-Fc, IL-15N72D:IL-15RaSu/Fc Fusion Complex, IL-15N72D:IL-15REC-SU/FC Soluble Complex I, Inbakicept Nogapendekin Alfa Fusion Complex, N 803, N-803, N803, Nogapendekin Alfa Inbakicept-pmln, Superagonist Interleukin-15:Interleukin-15 Receptor AlphaSu/Fc Fusion Complex Alt-803

Treatment (N-803, leukapheresis)

X-Ray Imaging PROCEDURE

Undergo chest x-ray

Also known as: Conventional X-Ray, Diagnostic Radiology, Medical Imaging, X-Ray, Plain film radiographs, Radiographic Imaging, Radiographic imaging procedure (procedure), Radiography, RG, Static X-Ray, X-Ray

Treatment (N-803, leukapheresis)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (N-803, leukapheresis)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically or cytologically confirmed synovial sarcoma (SS) and/or myxoid/round cell liposarcoma (MRCL) who have progressed after ACT using TCR-T
• Patients must have been treated with a TCR-T product that can be assessed per medical history and/or discretion of the principal investigator. This includes the Food and Drug Administration (FDA) approved Afamitresgene autoleucel but also other products at the discretion of the principal investigator.
• Note on references to Letetresgene Autoleucel and Afamitresgene Autoleucel: This study does not involve active treatment with TCR-T cell therapies, including Letetresgene autoleucel or Afamitresgene autoleucel. The investigational drug of this study is N-803
• Patients must have measurable disease according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
• Patients must have shown clinical benefit on at least one scan post ACT using TCR-T, (stable disease \[SD\], partial response \[PR\], complete response \[CR\]), as determined by the treating investigator
• Patients must be aged ≥ 18 to 80 at time of registration
• Patients must have a performance status of \> 70% on the Karnofsky scale or \< 2 on the Eastern Cooperative Oncology Group (ECOG) performance scale
• Patients must be able to undergo leukapheresis per institutional standards. For patients receiving leukapheresis at the Rube Walker Blood Center, reference document guidance and Rube Walker Blood Center leukapheresis eligibility criteria
• Absolute lymphocyte count (ALC) ≥ Institutional lower limit of normal (within screening window of 28 days up until pre-dose leukapheresis)
• Absolute neutrophil count (ANC) ≥ 1,000/mcL (within screening window of 28 days up until pre-dose leukapheresis)
• Prior growth factors are allowed per treating investigator discretion (i.e. erythropoietin \[EPO\]), granulocyte-macrophage colony-stimulating factors (GM-CSF) such as sargramostim, platelet-derived growth factor (PDGF), granulocyte colony-stimulating factors (G-CSF) including filgrastim, darbepoetin alfa are allowed per standard of care
• Hemoglobin (Hgb) ≥ 8.3 g/dL (within screening window of 28 days up until pre-dose leukapheresis)
• Platelets (PLT) ≥ 40,000/mcL (within screening window of 28 days up until pre-dose leukapheresis)
• Total bilirubin ≤ Institutional upper limit of normal (ULN) (within screening window of 28 days up until pre-dose leukapheresis)
• Unless the patient has documented Gilbert's syndrome. Patients with Gilbert syndrome may be eligible with total bilirubin up to 3 × ULN, provided direct bilirubin is within normal limits and per investigator discretion

You may not qualify if:

• Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1) with the exception of alopecia, neuropathy and other non-significant adverse events per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v 5.0) as deemed by the principal investigator
• Any medical diagnosis that would prevent the donation of white blood cells (WBCs) or patients whom in the opinion of the investigator should not donate WBCs
• Patients with high risk of bleeding, as determined by treating investigator.
• Note: If patients are on anticoagulants, the investigator will determine if patient can continue anticoagulants throughout the study, or if their dosage needs to be changed until completion of both leukapheresis procedures
• Patients with illnesses or conditions that would prevent them from taking blood thinners or patients whom in the opinion of the investigator should not take blood thinners
• Patients who have received other IL-15 treatments since receiving TCR-T cells to the start of study treatment (C1D1).
• Note: Prior growth factors are allowed per treating investigator discretion (i.e. erythropoietin (EPO), granulocyte-macrophage colony-stimulating factors (GM-CSF) such as sargramostim, platelet-derived growth factor (PDGF), granulocyte colony-stimulating factors (G-CSF) including filgrastim, darbepoetin alfa
• Patients with new or progressing brain metastases.
• Note: Patients with treated brain metastases that are stable in the opinion of the treating investigator are eligible
• Known significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within 3 months prior to pre-dose leukapheresis, unstable arrhythmias, or unstable angina. To be eligible for this trial, patients should be class 2B or better
• 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
• Participants who, in the opinion of the investigator, are unable to safely or feasibly receive subcutaneous injections of N-803. Examples include:
• Absence of suitable subcutaneous tissue for injection (e.g., due to cachexia, scarring, or anatomical limitations).
• Known 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.
• Active skin conditions or infections at potential injection sites.

Sponsors & Collaborators

• Northwestern University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Northwestern University

Chicago, Illinois, 60611, United States

RECRUITING

MeSH Terms

Conditions

Liposarcoma, Myxoid; Sarcoma, Synovial

Interventions

Specimen Handling; Leukapheresis; Magnetic Resonance Spectroscopy; ALT-803; X-Rays; Phantoms, Imaging

Condition Hierarchy (Ancestors)

Liposarcoma; Neoplasms, Adipose Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Neoplasms, Connective Tissue

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Cytapheresis; Biological Therapy; Therapeutics; Blood Component Removal; Leukocyte Reduction Procedures; Cell Separation; Cytological Techniques; Spectrum Analysis; Chemistry Techniques, Analytical; Electromagnetic Radiation; Electromagnetic Phenomena; Magnetic Phenomena; Physical Phenomena; Radiation; Radiation, Ionizing; Equipment and Supplies

Study Officials

• Seth M Pollack, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Study Coordinator

CONTACT

3126951301; cancer@northwestern.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 21, 2025
• First Posted: December 3, 2025
• Study Start: April 13, 2026
• Primary Completion (Estimated): September 2, 2030
• Study Completion (Estimated): September 2, 2032
• Last Updated: May 5, 2026

Record last verified: 2026-04

Locations

US (1)