Study of NXC-201 CAR-T in Patients With Light Chain (AL) Amyloidosis

Open-label Phase 1b Dose Escalation/Dose Expansion study exploring the safety and efficacy of NXC-201 in patients with relapsed or refractory light chain amyloidosis (AL).

Inclusion Criteria: 1. ≥18 years of age. 2. Voluntarily signed informed consent form (ICF). 3. Eastern Cooperative Oncology Group (ECOG) performance status 0-2. 4. Histologically proven systemic AL amyloidosis confirmed by positive Congo red staining with green birefringence on polarized light microscopy in an organ outside the bone marrow and evidence of a measurable clonal plasma cell disease that requires active treatment. 1. An underlying plasma cell disorder can be identified by one of the following: clonal plasma cells in the BM, monoclonal protein in the serum or urine, or abnormal free light chain ratio. 2. Because AL amyloidosis may present with low volumes of bone marrow plasma cells, prior biopsies demonstrating clonal plasma cell populations may be used to determine eligibility. 3. Measurable hematologic disease: difference between involved and uninvolved FLC \> 20 mg/L (or 2mg/dl) with an abnormal k/l ratio; or M-spike \> 0.5mg/dl. 5. Patients should have received at least one line of therapy with a CD38 monoclonal antibody and a proteosome inhibitor and not be in VGPR or CR at the time of inclusion. Patients who did not reach VGPR after two cycles of initial therapy or patients who did achieve VGPR or better but with a hematological relapse can be included. 6. Symptomatic organ involvement (heart, kidney, liver/GI tract, peripheral nervous system). 7. Women of child-bearing potential (WCBP) must have a negative serum pregnancy test prior to treatment. All sexually active WCBP and all sexually active male subjects must agree to use effective methods of birth control throughout the study. 8. Recovery to ≤Grade 2 or baseline of any non-hematologic toxicities due to prior treatments, excluding alopecia and Grade 3 neuropathy. 9. Absence of any psychological, familial, sociological, or geographical conditions potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before trial entry. 10. Able to swallow pills. Exclusion Criteria: 1. Prior treatment with CAR T therapy directed at any target. 2. Any therapy that is targeted to BCMA. 3. Stroke or seizure within 6 months of signing ICF. 4. Bone marrow plasma cells \>30% and clinically symptomatic multiple myeloma with end organ damage (i.e. lytic bone lesions). 5. New York Heart Association Heart Failure Class III or Class IV. 6. Any prior systemic therapy for AL amyloidosis within 14 days prior to leukapheresis. 7. Therapeutic doses of steroids within 2 weeks prior to leukapheresis (Physiological replacement doses of steroids are allowed up to 12 mg/m2/d hydrocortisone or equivalent). 8. Any prior systemic therapy for AL amyloidosis within 14 days of leukapheresis. 9. Wash-out period of at least 4 weeks from previous investigational treatment prior to leukapheresis. 10. Inadequate hepatic function: 1. Aspartate aminotransferase (AST \[SGOT\] or alanine aminotransferase (ALT \[SGPT\]) \>3 x upper limit of normal (ULN) value 2. Alkaline phosphatase \>2 times ULN 3. Serum direct bilirubin \>2 times ULN 11. Inadequate renal function: creatinine clearance (CRCL) \1.5 x ULN, unless on a stable dose of anticoagulant for a thromboembolic event that does NOT meet exclusion criteria. 13. Inadequate bone marrow function prior to leukapheresis or lymphodepletion, without transfusion or growth factor support within 5 days prior defined by absolute neutrophil count (ANC) \