A Clinical Study of CT0596 CAR-T in Relapsed/Refractory Multiple Myeloma

Phase I employs a BOIN design for dose escalation to determine the maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D). Phase II will further confirm the clinical efficacy of CT0596 at the RP2D in R/R MM, with the primary efficacy endpoint being the overall response rate (ORR) at Week 12 post-infusion, assessed by an Independent Review Committee (IRC) per International Myeloma Working Group(IMWG) 2016 criteria.

Inclusion criteria

• Voluntarily participate in the trial; fully understand and sign the informed consent form (ICF); willing and able to comply with all trial procedures.
• Age ≥ 18 years, male or female.
• Patients with relapsed/refractory multiple myeloma (R/R MM) who have received at least 3 prior lines of therapy, including at least one proteasome inhibitor (PI), at least one immunomodulatory agent (IMiD), and at least one anti-CD38 monoclonal antibody.
• Relapsed/refractory disease defined per IMWG 2016 response criteria,.
• Must have measurable disease:
• Life expectancy ≥ 12 weeks.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Must have Adequate organ function
• Female participants of childbearing potential must have a negative pregnancy test at screening and prior to lymphodepletion, and must agree to use highly effective contraception for at least 1 year after CT0596 infusion, and absolutely refrain from oocyte donation. Male participants with active sexual life with WOCBP must agree to use highly effective contraception for at least 1 year after infusion and absolutely refrain from sperm donation。

Exclusion criteria

• Pregnant or lactating women.
• Positive for HIV, syphilis, active hepatitis B (HBV-DNA above LLoD), or active hepatitis C (positive for both HCV antibody and HCV-RNA).
• Presence of any uncontrolled active infection, including but not limited to active tuberculosis (per investigator), active CMV and/or EBV infection, etc.
• Toxicity from prior therapy not recovered to ≤ Grade 1 per Common Terminology Criteria for Adverse Events(CTCAE) V5.0 (except alopecia and other events deemed tolerable by the investigator).
• Prior BCMA-targeted therapy (refer to the protocol for exceptions).
• Prior allogeneic stem cell transplantation; or autologous SCT within 3 months prior to signing ICF; or planned Hematopoietic Stem Cell Transplantation(HSCT) during the trial.
• Received disease-directed therapy within 14 days or 5 half-lives (whichever is shorter) prior to lymphodepletion.
• Received any cell therapy within 6 months prior to ICF; or prior CAR-T with best response < PR.
• Received systemic corticosteroids equivalent to > 15 mg/day of prednisone within 7 days prior to lymphodepletion (excluding topical use).
• Received live-attenuated, inactivated, or RNA vaccines within 4 weeks prior to lymphodepletion.
• Major surgery within 2 weeks prior to lymphodepletion, or planned major surgery during trial or within 4 weeks after treatment (excluding local anesthesia surgeries).
• Allergy or intolerance to lymphodepletion agents, tocilizumab, or any component of infusion (e.g., DMSO); or history of severe allergy such as anaphylactic shock.
• Diagnosed with secondary plasma cell leukemia, solitary extramedullary plasmacytoma, Waldenström macroglobulinemia, POEMS syndrome, or primary light chain amyloidosis at screening.
• Severe cardiac diseases within 6 months prior to screening.
• Severe pulmonary disease that may jeopardize the patient's life per investigator.
• Inability to tolerate an adequate lymphodepletion regimen.
• Secondary primary malignancy requiring treatment or not in complete remission within 2 years prior to screening, except for successfully treated non-metastatic basal/squamous cell skin carcinoma, non-metastatic prostate cancer, carcinoma in situ (breast/cervix), non-muscle-invasive bladder cancer, or low-grade thyroid cancer.
• Known symptomatic central nervous system (CNS) disease or suspected CNS metastasis.
• Patients assessed by the investigator as unable or unwilling to comply with protocol requirements, or otherwise unsuitable for participation.