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

Inclusion Criteria: * 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 * Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]) ≤ 1.5 x institutional ULN (within screening window of 28 days up until pre-dose leukapheresis) * Alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) ≤ 1.5 x institutional ULN (within screening window of 28 days up until pre-dose leukapheresis) * Alkaline phosphatase (ALP) ≤ 2.5 institutional ULN (within screening window of 28 days up until pre-dose leukapheresis) * Serum creatinine ≤ 2.0 mg/dL or 177 μmol/L or creatinine clearance ≥ 40 mL/min (using the Cockcroft-Gault formula) (within screening window of 28 days up until pre-dose leukapheresis) * Note: All laboratory value permitted departures (described in the above table with a different ULN) should be clearly documented by the treating investigator in the sources * Note: Patients do not need to meet lab eligibility requirements after screening. For days of leukapheresis, refer to institutional guidelines for lab eligibility for leukaphereses (see Rube Walker Blood Center leukapheresis eligibility criteria) * Note: The institutional upper limit refers to the reference range upper limit established by the institution where the laboratory tests were performed * The effects of N-803 on the unborn fetus are unknown. For this reason, patients of child-bearing potential (POCBP) and their partners with sperm-producing reproductive capacity must agree to use adequate contraception from start of treatment, for the duration of study participation, and for 7 months following completion of N-803 therapy. Should a POCBP become pregnant or suspect they are pregnant while they or their partner are participating in this study, they should inform their treating physician immediately. Patients with sperm-producing reproductive capacity (PWSPRC) treated or enrolled on this protocol must also agree to use adequate contraception with partners of childbearing potential from time of informed consent, for the duration of study participation, and 7 months after completion of administration * Note: A POCBP is any patient (regardless of gender, sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) with an egg-producing reproductive tract who meets the following criteria * Has not undergone a hysterectomy or bilateral oophorectomy * Has had menses at any time in the preceding 12 consecutive months (and therefore has not been naturally postmenopausal for \> 12 months) * POCBP must have a negative pregnancy test during screening and per the study schedule. See study procedures for more information * Patients must have the ability to understand and the willingness to sign a written informed consent document and comply with the study requirements Exclusion Criteria: * 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. * Physical or psychological inability to tolerate subcutaneous injection procedures (e.g., severe needle phobia, movement disorders). * Medical contraindications to subcutaneous administration (e.g., bleeding disorders, severe dermatologic conditions). * Any other factors that, in the judgment of the investigator, would interfere with safe and feasible administration of subcutaneous injections * Major surgical procedure (e.g., gastrointestinal \[GI\] surgery, removal or biopsy of brain metastasis), other than for diagnosis or known need for a major surgical procedure while on study treatment. * Note: Patients must have fully recovered from complete wound healing from said surgery prior to first study assessment, in the opinion of the treating investigator. * Note: Surgery and radiation are allowed after completion of cycle 5 per discretion of treating investigator (CT scan and N-803 administration at cycle 5 must have already occurred) * Systemic autoimmune disease currently requiring treatment (e.g., lupus erythematosus, rheumatoid arthritis, Addison's disease, or autoimmune disease associated with lymphoma). The patient must have been off treatment for 90 days from registration * History of organ transplant requiring immunosuppression; or history of pneumonitis or interstitial lung disease requiring treatment with systemic steroids; or a history of receiving systemic steroid therapy or any other immunosuppressive medication ≤ 3 days prior to study initiation. Daily steroid replacement therapy (e.g., prednisone or hydrocortisone at doses of ≤ 10 mg/day of prednisone (or equivalent)) and corticosteroids used to manage adverse events (AEs) are permitted. Patients who require immunosuppressive agents during their study participation are ineligible, except: * Use of physiologic doses of systemic steroid replacement is permitted at doses of ≤ 10 mg/day of prednisone (or equivalent, e.g., dexamethasone 1.5 mg, methylprednisolone 8 mg, or hydrocortisone 40 mg). * Local steroids, including topical steroids (e.g., hydrocortisone, clobetasol), nasal steroids (e.g., fluticasone, mometasone), or inhaled steroids (e.g., budesonide, beclomethasone). * Limited courses (\< 1 week) of systemic steroids (≤ 10 mg/day of prednisone or equivalent) (e.g, in patients with exacerbations of reactive airway disease or anaphylaxis in patients who have known contrast allergies). * Immunosuppressive treatments to optimally manage immune-related AEs as clinically indicated * Serious uncontrolled concomitant disease that would contraindicate the use of the investigational drug used in this study or that would put the patient at high risk for treatment-related complications * Patients who have an uncontrolled intercurrent illness including, but not limited to any of the following: * Hypertension that is not controlled on medication * Ongoing or active infection requiring systemic treatment including: * Known active infection with acute or chronic hepatitis B or C, known active human immunodeficiency virus (HIV), or acquired immunodeficiency syndrome * Exception: uncomplicated urinary tract infections (or sinus infections and are on antibiotics) * (AIDS)-related illness * Symptomatic congestive heart failure * Unstable angina pectoris * Cardiac arrhythmia * Psychiatric illness/social situations that would limit compliance with study requirements * Any other illness or condition that the treating investigator feels would interfere with study compliance or would compromise the patient's safety or study endpoints * Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen except the following: * Basal cell carcinoma of the skin * Squamous cell carcinoma of the skin * In situ cervical cancer that has undergone potentially curative therapy * Patient is pregnant or nursing. * Note: Pregnant patients are excluded from this study because N-803 is an interleukin-15 (IL-15) receptor agonist with potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with N-803, breastfeeding should be discontinued if the mother is treated with N-803 * Note: Serum test will be conducted at screening (serum pregnancy test \[beta-human chorionic gonadotropin \[β-HCG\]) * Other conditions which, in the opinion of the Investigator, would compromise the safety of the patient or the patient's ability to complete the study * Patients who need to be on concurrent anticancer treatment (e.g., chemotherapy, immunotherapy, cytokine therapy \[except erythropoietin\]) throughout participation in the study * Patients who have had prior use of narrow therapeutic index drugs that are substrates of major CYP450 enzymes within 28 days of first study drug administration per discretion of the treating investigator, including but not limited to: * Tacrolimus * Cyclosporine * Sirolimus * Everolimus * Warfarin * Phenytoin * Midazolam * Tamoxifen * Codeine * Erlotinib * Patients who have had prior use concomitant medications that prolong the QT/corrected QT (QTc) interval within 28 days of first study drug administration visit per discretion of the treating investigator * Patients who have had prior biologic therapies or chemotherapy within 28 days of pre-dose leukapheresis visit, or radiation therapy within 14 days of pre-dose leukapheresis visit * Patient must have reviewed and signed the informed consent document before any study activities may occur. Registration of patients is completed in NOTIS