A Pilot Trial of N-803 in Patients With Synovial Sarcoma and Myxoid/Round Cell Liposarcoma Previously Treated With Adoptive Cellular Therapy
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.
∙ 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. Please see Section 4.3.3 for more information.
• 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 must be aged ≥ 18 to 80 at time of registration.
• Patients must have a performance status of \>70% on the Karnofsky Scale (see Appendix A) or \< 2 on the ECOG Performance Scale (see Appendix B).
• Patients must be able to undergo leukapheresis per institutional standards. For patients receiving leukapheresis at the Rube Walker Blood Center, see Appendix F for reference document guidance and Rube Walker Blood Center leukapheresis eligibility criteria.
• Patients must have adequate organ and bone marrow function as defined below within screening window of 28 days up until Pre-Dose Leukapheresis:
∙ Laboratory Test Value
∙ Absolute Neutrophil Count (ANC) ≥ 1,000/mcL\*\* Hemoglobin (Hgb) ≥ 8.3 g/dL Platelets (PLT) ≥ 40,000/mcL Total bilirubin ≤ Institutional upper limit of normal (ULN)\* AST (SGOT) ≤ 1.5 x institutional ULN ALT (SGPT) ≤ 1.5 x institutional ULN ALP (alkaline phosphatase) ≤ 2.5 institutional ULN Serum Creatinine ≤ 2.0 mg/dL or 177 μmol/L or creatinine clearance ≥ 40 mL/min (using the Cockcroft-Gault formula below):
∙ Cockcroft-Gault Formula:
∙ Female = \[(140 - age in years) × weight in kg × 0.85\] / \[72 × serum creatinine in mg/dL\]
∙ Male = \[(140 - age in years) × weight in kg × 1.00\] / \[72 × serum creatinine in mg/dL\]
∙ \*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.
∙ \*\* 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. Refer to Section 4.2 for more information on supportive care measures.
∙ 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 Appendix F for 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 in Section 5 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.