Safety and Efficacy of CS1 CAR-T (WS-CART-CS1) in Subjects With Multiple Myeloma

Prior treatment

• Any prior systemic therapy for multiple myeloma within 14 days before planned day of leukapheresis.
• Currently receiving any other investigational agents.
• Receipt of any cellular therapy within 8 weeks prior to the planned start of conditioning.

Other illness

• A history of other malignancy with the exception of treated non-melanomatous skin cancers and malignancies for which all treatment was completed at least 2 years before registration and the subject has no evidence of disease.
• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to CS1 CAR-T or other agents used in the study.
• History of Grade 3 CRS or ICANS with other CAR-Ts (including BCMA CAR).
• Active hepatitis B, active hepatitis C, any uncontrolled infection, or HIV infection.
• Ongoing or active infection or other serious underlying medical condition that would impair the ability to receive protocol treatment.

Other

• Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 14 days of study entry.

• Relapsed or refractory multiple myeloma after 3 or more prior lines of therapy, including proteasome inhibitor (e.g. bortezomib or carfilzomib), anti-CD38 therapy (e.g. daratumumab), and anti-BCMA therapies (e.g. BCMA bispecific antibodies or BCMA CAR-T)
• Measurable disease, defined as meeting at least one of the following criteria:
  • Serum M-protein ≥ 0.5 g/dL
  • Urine M-protein ≥ 200 mg/24 h
  • In patients without measurable serum and urine M-protein levels, the difference between involved and uninvolved FLC levels (absolute increase) must be \>10 mg/dL for consideration of defining progression before enrollment
  • A biopsy-proven plasmacytoma
  • Bone marrow plasma cells \> 30% of total bone marrow cells
• At least 18 years of age.
• ECOG performance status ≤ 1
• Adequate renal, hepatic, respiratory, and cardiovascular function, as defined below:
  • Renal function:
  • calculated creatinine clearance ≥ 50 mL/min/1.73 m2 OR
  • radioisotope glomerular filtration rate ≥ 50 mL/min/1.73 m2 OR
  • normal serum creatinine based on age/gender per institutional normal range
  • Hepatic function:
  • ALT (SGPT) ≤ 5 x ULN for age
  • Total bilirubin ≤ 2.0 x IULN (unless the patient has Grade 1 bilirubin elevation due to Gilbert's disease or a similar syndrome involving slow conjugation of bilirubin)
  • Respiratory function:
  • Minimum level of pulmonary reserve defined as oxygen saturation \> 91% measured by pulse oximetry on room air
  • Cardiovascular function:
  • LVEF ≥ 45% confirmed by echocardiogram or MUGA within 28 days of screening
• The effects of CS1 CAR-T on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception (at least 2 forms of contraception, including one barrier method) prior to study entry and for 12 months after CS1 CAR-T infusion. If a female subject or female partner of a male subject becomes pregnant during therapy or within 12 months following WS-CART-CS1 infusion, the investigator must be notified in order to facilitate outcome follow-up.
• Ability to understand and willingness to sign an IRB-approved written informed consent document (or that of legally authorized representative, if applicable).