A Study of CAR-T Cells Targeting Both BCMA and GPRC5D in Treatment of Relapsed or Refractory Multiple Myeloma

Study Overview
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Brief Summary
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An Open-Label, Dose Finding Study to Investigate the Safety, Pharmacokinetics, and Preliminary Efficacy of BMCA and GPRC5D dual target CAR-T cells therapy in Patients with relapsed or refractory multiple myeloma

Official Title
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An Open-Label, Dose Finding Study to Investigate the Safety, Pharmacokinetics, and Preliminary Efficacy of BMCA and GPRC5D Dual Target CAR-T Cells Therapy in Patients With Relapsed or Refractory Multiple Myeloma

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Biological: BMCA and GPRC5D dual target CAR-T cells(OriC321)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed and dated, written informed consent prior to any study specific procedures; Estimated life expectancy of minimum of 12 weeks; ECOG 0-2; Diagnosed as multiple myeloma according to the IMWG criteria; Evidence of cell membrane GPRC5D and/or BCMA expression, as determined by a validated immunohistochemistry (IHC) or flow cytometry of tumor tissue; Subjects should have measurable disease. At least meet one of the following criteria: If IgG type MM, serum M protein ≥10g/L; if IgA, IgD, IgE or IgM type MM, serum M protein ≥5g/L; urine M protein level ≥0.2g(200mg/24h); light chain type MM, serum free light chain (sFLC) ≥ 100mg / L and K/ λ FLC ratio is abnormal; there are extramedullary lesions; Subjects have had at least 3 prior lines of therapy including chemotherapy based on proteasome inhibitors (PIs) and immunomodulatory agents (IMiDs); Adequate organ functions Exclusion Criteria: Active smoldering multiple myeloma; Active plasma cell leukemia; With organ amyloidosis; Central nervous system (CNS) involvement; Pregnant or breastfeeding; Hepatitis B virus (HBV) surface antigen (HBsAg) or hepatitis B core antibody-positive and detectable HBV DNA in peripheral blood; Hepatitis C virus (HCV) antibody and hepatitis C virus RNA in peripheral blood; Human immunodeficiency virus (HIV) antibody Uncontrolled Hypertension hypertension defined as a blood pressure (BP) ≥150/95 mmHg; Symptomatic heart failure per New York Heart Association Classification Class II, III or IV), Mean resting corrected QT interval corrected by Fridericia's formula (QTcF) > 470 msec (female), 450 msec (male) obtained from ECG; Baseline left ventricular ejection fraction (LVEF) below institution's lower limit of normal (LLN) or <50%; Have a history of another primary malignancy within 5 years prior to starting study treatment. Exceptions here are as follows: the disease under study; adequately treated basal or squamous cell carcinoma of the skin; cancer of the cervix in situ.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BMCA and GPRC5D dual target CAR-T cells （OriC321）<br> | Biological: BMCA and GPRC5D dual target CAR-T cells(OriC321)<br>* Patients will receive lymphodepleting chemotherapy followed by a single infusion of OriC321<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence, severity AEs/SAEs |  | 2 years after CAR-T cell infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of CAR-T cells |  | 2 years after CAR-T cell infusion | 
| Objective response rate (ORR) |  | 2 years after CAR-T cell infusion | 
| Progression-free survival (PFS) |  | 2 years after CAR-T cell infusion | 
| Duration of response (DOR) |  | 2 years after CAR-T cell infusion | 
| Overall survival (OS) |  | 2 years after CAR-T cell infusion | 
| Percentage of Patients With Negative Minimal Residual Disease (MRD) |  | 2 years after CAR-T cell infusion |