Clinical Trial to Evaluate Zevor-cel (CT053) in Patients With Relapsed and/or Refractory Multiple Myeloma (LUMMICAR STUDY 2)

This is an open label, multi-center, phase 1b/2 clinical trial to evaluate the safety and efficacy of autologous chimeric antigen receptor-B-cell maturation antigen (CAR-BCMA T cell; zevor-cel/CT053) in patients with relapsed and or refractory multiple myeloma.

Phase 1b of the study will be dose escalation followed by an expansion cohort. After recommended Phase 2 dose is identified in Phase 1b, the enrollment of Phase 2 will start. Following consent, enrolled subjects will undergo a leukapheresis procedure to collect autologous mononuclear cells for manufacture of investigational drug product (zevor-cel). Following manufacture of the drug product, subjects will receive lymphodepletion prior to zevor-cel infusion. All subjects who complete the study, as well as those who withdraw from the study after receiving zevor-cel for reasons other than death or meeting the early termination criteria, will be asked to continue to undergo a 15-year long-term follow-up study.

Inclusion criteria

• Voluntarily signed consent;
• Age of ≥ 18 and < 80 years;
• Received sufficient prior lines of myeloma therapy;
• Received treatment with at least one proteasome inhibitor, one IMiD and CD38 anti body.
• The patient must be refractory to the last line of therapy.
• The patients should have measurable disease per IMWG definition.
• Estimated life expectancy > 12 weeks;
• ECOG performance score 0-1;
• Patients should have reasonable CBC counts, renal and hepatic functions;
• Sufficient venous access for leukapheresis collection, and no other contraindications to leukapheresis;
• Women of childbearing age must undergo a serum pregnancy test with negative results before screening, and are willing to use effective and reliable method of contraception for at least 12 months after T cell infusion;
• Men must be willing to use effective and reliable method of contraception for at least 12 months after T cell infusion.

Exclusion criteria

• Pregnant or lactating women;
• HIV, active hepatitis C virus (HCV), or active hepatitis B virus (HBV) infection;
• Any uncontrolled active infection;
• AEs from previous treatment that have not recovered;
• Patients who have had anti-BCMA therapy;
• Patients who have graft versus host disease (GvHD);
• Patients have received stem cell transplantation one year before leukapheresis;
• Patients have received any anti-cancer treatment before leukapheresis;
• Patients have received steroids before leukapheresis or lymphodepletion;
• Patients have plasma cell leukemia, Waldenström macroglobulinemia, POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome or clinically significant symptomatic immunoglobulin light chain (AL) amyloidosis with evidence of end-organ damage;
• Patients have been administered live attenuated vaccine before leukapheresis or lymphodepletion;
• Patients allergic to Flu, Cy, tocilizumab, dimethyl sulfoxide (DMSO) or zevor-cel CAR BCMA T cell;
• Patients have clinical significant cardiac conditions that researchers believe that participating in this clinical trial may endanger the health of the patients;
• Patients have clinical significant pulmonary conditions;
• Patients are known to have active autoimmune diseases including but not limited to psoriasis, rheumatoid arthritis and other needs of long-term immunosuppressive therapy;
• Patients with second malignancies in addition to MM are not eligible;
• Patients have central nervous system (CNS) metastases or CNS involvement;
• Patients have significant neurologic disorders;
• Patients are unable or unwilling to comply with the requirements of clinical trial;
• Patients have received major surgery prior to leukapheresis or prior to lymphodepletion.