APRIL CAR T Cells (AUTO2) Targeting BCMA and TACI for the Treatment of Multiple Myeloma

A Single-Arm, Open-Label, Multi-Centre, Phase I/II Study Evaluating the Safety and Clinical Activity of AUTO2, a CAR T Cell Treatment Targeting BCMA and TACI, in Patients With Relapsed or Refractory Multiple Myeloma

The purpose of this study is to test the safety and efficacy of AUTO2, a CAR T Cell Treatment Targeting BCMA and TACI, in Patients with Relapsed or Refractory Multiple Myeloma.

The study will consist of 2 phases, a Phase I/dose escalation phase and a Phase II/expansion phase. Patients with relapsed and relapsed or refractory multiple myeloma will be enrolled in both phases of the study. Eligible patients will undergo leukapheresis in order to harvest T cells, which is the starting material for the manufacture of the autologous CAR T product AUTO2. AUTO2 has a dual target BCMA (B cell maturation antigen) and TACI (Transmembrane activator and calcium modulator and cyclophilin ligand interactor). Following pre-conditioning by a chemotherapeutic regimen, the patient will receive AUTO2 intravenously as a single or split dose and will then enter a 12-month follow-up period.

Key Inclusion Criteria:

1. Male or female patients, aged ≥ 18.
2. Willing and able to give written, informed consent.
3. Confirmed diagnosis of MM.
4. Measurable disease as defined by IMWG.
5. Relapse or refractory disease and have had at least 3 different prior lines of therapy including proteasome inhibitor, alkylator and immunomodulatory therapy (IMiD), or have "double refractory" disease to a proteasome inhibitor and IMiD.
6. For females of childbearing potential, a negative serum or urine pregnancy test must be documented at screening and confirmed before receiving study treatment.
7. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 1.
8. Peripheral blood total lymphocyte count > 0.5 x 10⁹/L.

Key Exclusion Criteria:

1. Women who are pregnant or lactating.
2. Prior treatment with investigational or approved gene therapy or cell therapy products.
3. Patient has previously received an allogenic stem cell transplant.
4. Clinically significant, uncontrolled heart disease or a recent (within 6 months) cardiac event.
5. Left Ventricular Ejection fraction < 50 unless the institutional lower limit of normal is lower.
6. Significant liver disease: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 3 × ULN, or total bilirubin > 2.0 mg/dL or evidence of end stage liver disease (e.g. ascites, hepatic encephalopathy).
7. Chronic renal impairment requiring dialysis, or calculated creatinine clearance < 30 mL/min
8. Active infectious bacterial or viral disease (hepatitis B virus, hepatitis C virus, human immunodeficiency virus, human T-lymphotropic virus or syphilis) requiring treatmenUse of rituximab within the last 3 months.
9. Active autoimmune disease requiring immunosuppression.
10. Received any anti-myeloma therapy within the last 21 days prior to preconditioning or 10 days prior to leukapheresis; steroids of up to 160 mg of dexamethasone are permitted so long as > 7 days post-dose prior to pre-conditioning or leukapheresis.
11. Known allergy to albumin, dimethyl sulfoxide (DMSO), cyclophosphamide or fludarabine.