A Phase 1 Safety and Efficacy Study of JV-394 Autologous Anti-CD94 Chimeric Antigen Receptor T Cell Therapy in Patients With Relapsed or Refractory CD94+ T/NK Cell Neoplasms
The goal of this clinical research study is to find the highest tolerable dose of JV-394 (a type of autologous CAR-T cell therapy) that can be given to patients who have T/NK cell lymphoma that is relapsed or refractory. The safety and possible side effects of JV-394 will also be studied.
• ≥18 years of age.
• Confirmed T/NK cell malignancies as per local histopathological assessment.
• Relapsed or refractory disease after at least one line of systemic therapy or intolerant to standard therapy for their cancer.
• Eligible histologies include: extranodal NK/TCL, hepatosplenic TCL, primary cutaneous CD8+ aggressive epidermotropic cytotoxic TCL, subcutaneous panniculitis-like TCL, monomorphic epitheliotropic intestinal TCL, enteropathy-associated TCL, primary cutaneous γδ TCL, peripheral TCL cytotoxic type, Epstein-Barr virus (EBV)+ nodal T/NK cell lymphoma, and other CD94+ T/NK cell malignancies not listed above.
• ≥50% of tumor cells are positive for CD94 by flow cytometry or IHC. Historical documentation of CD94 expression in the tumor is acceptable if available. If there is no historical documentation of CD94 expression, testing of archival tumor tissue or fresh tumor biopsy is required. Testing of archival tumor tissue may be done by IHC following a prescreening consent.
• At least two weeks or 5 half-lives, whichever is shorter, must have elapsed since any prior systemic anti-cancer therapy or 1 week from prior radiation therapy prior to leukapheresis.
• ECOG performance status of 0-1 (Appendix 1).
• For non-cutaneous lymphomas, at least one measurable lesion as per Lugano 2014 classification. Subjects with primary cutaneous variants must have at least 1 measurable lesion that is evaluable using the Olsen 2021 criteria.
• Toxicities due to prior therapy must be stable and recovered to ≤grade 1 (except for clinically non-significant toxicities such as alopecia).
⁃ Absolute neutrophil count of ≥1.0×109 /L.
⁃ Absolute lymphocyte count of ≥0.1×109 /L.
⁃ Platelet count of ≥75×109 /L.
⁃ Creatinine clearance (as estimated by Cockcroft Gault) ≥45 mL/min.
⁃ Serum alanine transaminase (ALT) / aspartate transaminase (AST) ≤5 times the upper limit of normal (ULN).
⁃ Total bilirubin ≤2 mg/dL, except in patients with Gilbert's syndrome.
⁃ Cardiac ejection fraction ≥45% with no evidence of clinically significant pericardial effusion.
⁃ Baseline oxygen saturation ≥92% on room air.
⁃ Women of childbearing potential must have a negative serum or urine pregnancy test (women who have had hysterectomy and women who are over the age of 45 years and have not had a menstrual period for at least 1 year are not considered to be of childbearing potential).