A Pilot Trial of N-803: Patients With Synovial Sarcoma and Myxoid/Round Cell Liposarcoma Previously Treated With Adoptive Cellular Therapy

Background

Synovial sarcoma is an aggressive malignancy accounting for 5% to 10% of all soft-tissue sarcomas, usually arising near joints of the extremities.¹ First-line therapy involves surgical resection with adjuvant radiotherapy and chemotherapy.² Although synovial sarcoma can affect patients of any age, it most commonly affects adolescents and young adults. Myxoid/round cell liposarcoma (MRCL) accounts for 30% of liposarcomas and is characterized by the FUS-CHOP fusion gene, which produces an aberrant transcription factor.^3,4 MRCL predominantly affects young to middle-aged adults, with primary lesions often occurring in proximal extremities. Although both sarcomas currently have limited therapeutic options, emerging approaches may expand available treatments, most notably adoptive cell transfer (ACT) using T-cell receptor T-cell therapy (TCR-T).

ACT using TCR-T has already improved outcomes for many patients with otherwise incurable solid tumors, including melanoma, lung cancer, or sarcoma.^5-8 However, despite excellent overall response rates in the 50% range for patients with synovial sarcoma and MRCL in clinical trials,⁹ TCR-T responses were durable beyond 2 years in only 15% of patients with solid tumors and rarely complete.¹⁰ The mechanisms underlying disease progression after an initial TCR-T response remain unclear; however, high levels of persisting T cells are correlated with improved outcomes.^9,11-14 Interestingly, most patients who experience progression after ACT still have detectable TCR-T cells in their peripheral blood mononuclear cell (PBMC) post therapy, even at late time points.^15,16

In 2021, it was reported that PBMC from patients with synovial sarcoma and MRCL progressing after TCR-T have rare persisting cells (RPCs) with a unique, inert phenotype that can be activated to proliferate and lyse tumor targets using IL-15.⁸ These RPCs lack both classic exhaustion markers (PD-1, LAG-3) as well as markers of proliferation and activation (Ki67, CD39, etc). These results are consistent with prior murine studies, suggesting that IL-15 has substantial potential to stimulate TCR-T cells after ACT.^17-21

This pilot early phase 1 trial (NCT07261657) represents the first clinical effort to activate persisting transferred RPCs by using IL-15 superagonist N-803 (ImmunityBio) in patients who have progressed after TCR-T (Figure). Although this clinical trial will focus on synovial sarcoma and MRCL (both rare subtypes among the diseases most studied in TCR-T research), our conclusions will be broadly applicable across tumor types.

Inclusion Criteria

To enroll, patients must have histologically or cytologically confirmed synovial sarcoma and MRCL that progressed after ACT using TCR-T, have been treated with a TCR-T product that can be assessed per medical history and/or at the discretion of the principal investigator, and be aged 18 to 80 years at time of registration.

Study Sites, Patient Accrual Information, and Accrual Goal

This trial will be conducted at Northwestern University in Chicago, Illinois. The sample size is 8 patients.

Open Date and Percentage Accrued

This study opened April 13, 2026. Four patients have been screened, with 3 of these patients registered to the study as of late August 2026

Acknowledgements

This independent research is supported by ImmunityBio, Inc, through the supply of N-803. This research is also being funded by the Waterton-Adrienne Smith Sarcoma Research Fund.

Corresponding Author

Seth M. Pollack, MD,

Steven T. Rosen Professor of Cancer Biology, Cancer Immunology and Immunotherapy Initiative Coleader, Director of the Sarcoma Program, Lurie Cancer Center, Professor of Cancer Biology, Professor, Medicine (Hematology and Oncology), Northwestern University Feinberg School of Medicine, 303 E Superior St, #3-115, Chicago, IL 60611, seth.pollack@northwestern.edu, 312-503-5320

References

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