Study of Anitocabtagene-autoleucel in Relapsed or Refractory Multiple Myeloma (iMMagine-1)

Inclusion Criteria:

1. Age 18 years or older and has capacity to give informed consent
2. Relapsed or refractory multiple myeloma treated with at least 3 prior regimens ofsystemic therapy including proteasome inhibitor, immunomodulatory drugs (IMiD) andanti-CD38 antibody and are refractory to the last line of therapy. For each line, 2consecutive cycles are required unless the best response after 1 cycle was progressivedisease. Note: IMWG criteria defines refractory disease as disease progression on or within 60days of a therapy Note: Induction treatment with or without hematopoietic stem celltransplant and with or without maintenance is considered a single regimen
3. Documented measurable disease including at least one or more of the followingcriteria:
4. Serum M-protein ≥1.0 g/dL
5. Urine M-protein ≥200 mg/24 hours
6. Involved serum free light chain ≥10 mg/dL with abnormal κ/λ ratio (i.e., >4:1 or <1:2)
7. Eastern Cooperative Oncology Group (ECOG) performance status 0-1
8. Life expectancy >12 weeks
9. Adequate organ function defined as:
10. Oxygen (O2) saturation ≥92% on room air
11. Left Ventricular Ejection Fraction (LVEF) ≥45% by echocardiogram (ECHO) ormultigated acquisition (MUGA) scan
12. Absolute neutrophil count (ANC) ≥1.0k/µl, platelet count (PLT) ≥50k/µl, [NOTE: Platelet transfusion not allowed within 14 days; filgrastim (orbiosimilar) not allowed within 7 days, pegfilgrastim (or biosimilar) within 14days]
13. Creatinine clearance ≥45 mL/min min (as determined by the Cockgroft-Gaultequation) and not on dialysis
14. Aspartate transaminase (AST)/alanine transaminase (ALT) <3 x upper limits ofnormal (ULN)
15. Total bilirubin <1.5 x ULN (allow 3x ULN for Gilbert's syndrome)
16. Prothrombin time test (PTT), prothrombin time (PT)/international normalized ratio (INR) <1.5 x ULN, unless on a stable dose of anti-coagulant for a thromboembolicevent (Subjects with any history of thromboembolic stroke; or history or Grade 2 (G2) or greater hemorrhage within one year are excluded)
17. Resolution of adverse events (AEs) from any prior systemic anticancer therapy,radiotherapy, or surgery to Grade 1 or baseline (except G2 alopecia and G2 sensoryneuropathy)
18. Male and female participants of childbearing potential must agree to use highlyeffective methods of birth control through 12 months after the dose of study treatment
19. Willing to comply with and able to tolerate study procedures, including consent toparticipate in separate Long-term Safety Follow-up lasting up to 15 years per FDAguidance
20. Subject's leukapheresis product from non-mobilized cells is received and accepted forcell processing by manufacturing site. NOTE: Leukapheresis will be performed onlyafter all other eligibility criteria are confirmed

Exclusion Criteria:

1. Plasma cell leukemia or history of plasma cell leukemia
2. Treatment with the following therapies as specified below
3. Any prior systemic treatment for multiple myeloma within the 14 days prior toscheduled leukapheresis
4. Receiving high-dose (e.g., >10 mg prednisone or equivalent) systemic steroidtherapy or any other form of immunosuppressive therapy within 14 days prior toleukapheresis
5. Prior treatment with any gene therapy or gene-modified cellular immune-therapy
6. Prior B-cell maturation antigen (BCMA) directed therapy
7. Autologous stem cell transplantation within 3 months prior to leukapheresis, orany prior allogeneic stem cell transplantation
8. Subjects with solitary plasmacytomas without evidence of other measurable disease areexcluded
9. History of allergy or hypersensitivity to study drug components. Subjects with ahistory of severe hypersensitivity reaction to dimethyl sulphoxide (DMSO) are excluded
10. Contraindication to fludarabine or cyclophosphamide
11. Severe or uncontrolled intercurrent illness or laboratory abnormalities including
12. Active bacterial, viral, or fungal infection requiring systemic treatment (isolated fever may not constitute active infection in and of itself, (e.g.,related to disease)
13. Symptomatic congestive heart failure (i.e., New York Heart Association stage IIIor IV)
14. Unstable angina, arrhythmia, or myocardial infarction (MI) within 6 months priorto Screening
15. Significant pulmonary dysfunction
16. Uncontrolled thromboembolic events or recent severe hemorrhage (i.e., within oneyear)
17. Any history of pulmonary embolism (PE) in the past 12 months or deep veinthrombosis (DVT) within three months of enrollment. Therapeutic dosing ofanticoagulants (e.g., warfarin, low molecular weight heparin, Factor Xainhibitors) is allowed for history of PE/DVT if greater than twelve and threemonths, respectively, from time of enrollment, and should be at a stablemaintenance dose.
18. Auto-immune disease requiring immunosuppressive therapy within the last 24 months
19. Seropositive for and with evidence of active hepatitis B or C infection at time ofScreening, or HIV seropositive
20. Subjects with a history of hepatitis B but have received antiviral therapy andhave non-detectable viral DNA are eligible
21. Subjects seropositive because of hepatitis B virus vaccine with no signs oractive infection are eligible
22. Subjects who had hepatitis C but have received antiviral therapy and show nodetectable hepatitis C virus (HCV) viral RNA are eligible
23. Active central nervous system (CNS) involvement by malignancy
24. Any sign of active or prior CNS pathology including but not limited to history ofepilepsy, seizure, paresis, aphasia, stroke, subarachnoid hemorrhage or CNS bleed,severe brain injury, dementia, cerebellar disease, Parkinson's disease, organic brainsyndrome or psychosis
25. Active malignancy not related to myeloma that has required therapy in the last 3 yearsor is not in complete remission. Exceptions to this criterion include successfullytreated non-metastatic basal cell or squamous cell skin carcinoma, or prostate cancerthat does not require therapy.
26. Females who are pregnant or breastfeeding or females of childbearing potential notusing an effective method of birth control
27. Subjects with any significant medical condition, laboratory abnormality, orpsychiatric illness that would prevent the subject from participating in study (orfull access to medical records) as written including follow up, the interpretation ofdata or place the subject at unacceptable risk
28. Any vaccine ≤ 6 weeks before leukapheresis and/or anticipation of the need for such avaccine during the subject's participation in the study
29. Concurrent enrollment on another study using an investigational therapy for thetreatment of RRMM