A Study of C-CAR088 in Patients With Relapsed or Refractory Multiple Myeloma

Study Overview
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Brief Summary
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This is a multicenter, open-label study to evaluate the safety and efficacy of C-CAR088 in patients with relapsed or refractory multiple myeloma. The phase Ib part of this study is to determine the recommended phase 2 dose (RP2D) of C-CAR088 in the targeted patient population.

Detailed Description
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The study includes the following sequential procedures: Screening, Apheresis and C-CAR088 manufacturing, Baseline testing, Lymphodepletion, C-CAR088 infusion, and Follow-up Visit. Two dose levels of C-CAR088 will be tested during the phase Ib part to determine RP2D, which will be further evaluated during the phase II part.

Official Title
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A Phase Ib/II Study of CBM.BCMA Chimeric Antigen Receptor T Cell Product (C-CAR088) for Treating Patients With Relapsed or Refractory Multiple Myeloma

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Biological: B-cell maturation antigen (BCMA) directed chimeric antigen receptor (CAR)-T cell


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria ≥ 18 years of age, male or female patients Relapsed or refractory multiple myeloma Have been treated with ≥ 3 prior lines of therapy, including at least one proteasome inhibitor and one immunomodulatory drug, and had progressed during or within 12 months post the last treatment. Had measurable disease as defined by any of the following criteria: Serum M protein ≥ 0.5g/dL Urine M protein ≥ 200mg/24h Serum free light chain (sFLC): abnormal κ/λ ratio with involved sFLC ≥ 100mg/L Adequate liver, renal, bone marrow, and heart function Eastern cooperative oncology group (ECOG) 0-1 Exclusion Criteria Any known allergies to the components or excipients of the C-CAR088 cell product Prior allogeneic hematopoietic stem cell transplantation (HSCT) at anytime, or autologous stem-cell transplantation (ASCT) within 12 weeks prior to apheresis Central nervous system (CNS) involvement Stroke or convulsion history within 6 months prior to signing informed consent form (ICF) Plasma leukemia Autoimmune disease, immunodeficiency or diseases requiring immunosuppressants treatment Uncontrolled active infection; active hepatitis B virus (HBV), hepatitis C virus (HCV) infection; HIV or syphilis infection Severe heart, liver, renal or metabolism disease Inadequate wash-out time for previous anti-tumor treatments prior to apheresis Previous CAR-T cell treatment, genetically modified T-cell therapies or BCMA-directed treatment history History or current evidence of any condition, therapy, or laboratory abnormality that, in the opinion of the investigator, might confound the results of the trial, interfere with the patient's safe participation and compliance in the trial

Ages Eligible for Study
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Minimum Age: 18 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: C-CAR088<br>Autologous C-CAR088 administered by intravenous (IV) infusion | Biological: B-cell maturation antigen (BCMA) directed chimeric antigen receptor (CAR)-T cell<br>* Autologous 2nd generation BCMA-directed CAR-T cells, single infusion intravenously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| [phase Ib] Incidence and severity of Adverse Events | Incidence and severity of Adverse Events | 24 months | 
| [phase II] Overall response rate (ORR) at 3 months after C-CAR088 infusion | the rate of patients with best response of partial response (PR) or better at 3 months after C-CAR088 infusion | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate (ORR) | The rate of patients with best response of partial response (PR) or better | 24 months | 
| [phase Ib] Overall response rate (ORR) at 3 months after C-CAR088 infusion | The rate of patients with best response of partial response (PR) or better at 3 months after C-CAR088 infusion | 3 months | 
| Duration of response (DOR) | The time from the first documented PR or better response to relapse or death, whichever occurs first | 24 months | 
| Time to response (TTR) | The time from the date of C-CAR088 infusion to the first documented PR or better | 24 months | 
| Progression-free survival (PFS) | The time from the date of C-CAR088 infusion to the date of first documented disease progression or death | 24 months | 
| Overall survival (OS) | The time from the date of C-CAR088 infusion to the date of death | 24 months | 
| Minimal residual disease (MRD) negativity rate | The rate of patients reached MRD negativity | 24 months | 
| [phase II] Incidence and severity of Adverse Events | Incidence and severity of Adverse Events | 24 months | 
| Maximal plasma concentration (Cmax) | maximal plasma concentration of C-CAR088 in peripheral blood | 24 months | 
| Time to reach the maximal plasma concentration (Tmax) | Time to reach the maximal plasma concentration of C-CAR088 in peripheral blood | 24 months | 
| Area under the curve within 28 days (AUC0-28d) | Area under the curve of C-CAR088 in peripheral blood within 28 days post infusion | 28 days | 
| Time of last measurable observed concentration (Tlast) | Time of last measurable observed concentration of C-CAR088 in peripheral blood | 24 months | 
| Anti-drug (C-CAR088) antibody | Presence of serum anti-drug (C-CAR088) antibody | 24 months | 
| Serum M protein | serum M proteins concentration changes over time | 24 months | 
| Urine M protein | Urine M proteins concentration changes over time | 24 months | 
| Serum free light chain (sFLC) | Serum free light chain (sFLC) concentration changes over time | 24 months |