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

Inclusion Criteria:

• 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 BCMACAR-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

• Serum FLC assay: involved FLC level ≥10 mg/dL (100 mg/L) with abnormal serumFLC ratio

• 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 bilirubinelevation due to Gilbert's disease or a similar syndrome involving slowconjugation 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 (atleast 2 forms of contraception, including one barrier method) prior to study entryand for 12 months after CS1 CAR-T infusion. If a female subject or female partner ofa male subject becomes pregnant during therapy or within 12 months followingWS-CART-CS1 infusion, the investigator must be notified in order to facilitateoutcome follow-up.

• Ability to understand and willingness to sign an IRB-approved written informedconsent document (or that of legally authorized representative, if applicable).

Exclusion Criteria:

• Any prior systemic therapy for multiple myeloma within 14 days before planned day ofleukapheresis.

• A history of other malignancy with the exception of treated non-melanomatous skincancers and malignancies for which all treatment was completed at least 2 yearsbefore registration and the subject has no evidence of disease.

• Currently receiving any other investigational agents.

• Receipt of any cellular therapy within 8 weeks prior to the planned start ofconditioning.

• A history of allergic reactions attributed to compounds of similar chemical orbiologic 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 HIVinfection.

• Ongoing or active infection or other serious underlying medical condition that wouldimpair the ability to receive protocol treatment.

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