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.
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 FDA approved Afamitresgene autoleucel but also other products at the discretion of the principal investigator.
Patients must have measurable disease according to RECIST v1.1. See Appendix A for RECIST v1.1 criteria.
Patients must have shown clinical benefit on at least one scan post ACT using TCR-T, (SD, PR, CR), as determined by the treating investigator.
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 NCI CTCAE v 5.0 as deemed by the principal investigator.
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 who have received other IL-15 treatments since receiving TCR-T cells to the start of study treatment (C1D1).
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.
Single group
Biospecimen Collection
Procedure/SurgeryUndergo blood sample collection
Computed Tomography
Procedure/SurgeryUndergo CT
Leukapheresis
Procedure/SurgeryUndergo leukapheresis
Magnetic Resonance Imaging
Procedure/SurgeryUndergo MRI
Nogapendekin Alfa Inbakicept
Biological/VaccineGiven SC
X-Ray Imaging
Procedure/SurgeryUndergo chest x-ray
The expansion of rare persisting transferred T-cell receptor therapy
Will be assessed using T-cell receptor sequencing or flow cytometry.
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.
Overall response rate
Will be defined by Response Evaluation Criteria in Solid Tumors version 1.1. Will be estimated with a two-sided 95% confidence interval using the Clopper-Pearson method.
Six-month progression-free survival (PFS)
Defined as the proportion of patients who remain alive and progression-free at six months (± 2 weeks) from treatment initiation. The Kaplan-Meier method will be used to estimate the six-month PFS rate, and a corresponding 95% confidence interval will be reported.
Median PFS
Kaplan-Meier curves will be reported descriptively, and median PFS will only be interpreted if the survival function drops below 50% with sufficient events to support stable estimation.
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Seth Pollack
Lead sponsor
Northwestern University
Sponsor institution
National Cancer Institute (NCI)
Collaborator
