A Study of GC012F, a CAR T Therapy Targeting CD19 and BCMA in Subjects With Relapsed/Refractory Multiple Myeloma

Study Overview
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Brief Summary
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This trial is a phase 1b/2, open-label, multicenter study of GC012F, a CD19/BCMA dual CART-cell therapy, in adult subjects with relapsed/refractory Multiple Myeloma.

Detailed Description
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For Phase Ib It aims to evaluate the safety, tolerability, pharmacokinetic characteristics, pharmacodynamic effect, immunogenicity in subjects with relapsed/ refractory Multiple Myeloma, and determine the recommended Phase 2 dose of GC012F. For Phase 2, it aims to evaluate the efficacy, pharmacokinetic characteristics, pharmacodynamic effect, and immunogenicity, changes from baseline for subject-reported health-related quality of life, overall health status in subjects with relapsed/ refractory Multiple Myeloma.

Official Title
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A Phase 1b/2 Study of GC012F, a Chimeric Antigen Receptor T-cell (CAR T) Therapy Targeting CD19 and B-cell Maturation Antigen (BCMA) in Subjects With Relapsed/Refractory Multiple Myeloma

Conditions
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Relapsed/ Refractory Multiple Myeloma

Intervention / Treatment
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* Biological: GC012F


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females ≥18 years of age at the time of consent Written informed consent in accordance with federal, local, and institutional guidelines Have an ECOG performance status of 0 or 1 Documented diagnosis of MM per IMWG diagnostic criteria Received at least three prior MM treatment lines of therapy Have received as part of their previous therapy a PI and IMiD and an antiCD38 antibody. Have documented evidence of progressive disease by the IMWG criteria. Subjects must have measurable disease at screening. Adequate bone marrow and organ function Exclusion Criteria: Diagnosed or treated for invasive malignancy other than multiple myeloma, except: Malignancy treated with curative intent and with no known active disease present for ≥2 years before enrollment; or Adequately treated non-melanoma skin cancer without evidence of disease. The following cardiac conditions: New York Heart Association (NYHA) stage III or IV congestive heart failure Myocardial infarction or coronary artery bypass graft (CABG) ≤6 months prior to enrollment History of clinically significant ventricular arrhythmia or unexplained syncope, not believed to be vasovagal in nature or due to dehydration History of severe non-ischemic cardiomyopathy Received either of the following: An allogenic stem cell transplant within 6 months before apheresis. Subjects who received an allogeneic transplant must be off all immunosuppressive medications for 6 weeks without signs of graft-versus-host disease (GVHD). An autologous stem cell transplant ≤12 weeks before apheresis Known active, or prior history of central nervous system (CNS) involvement or exhibits clinical signs of meningeal involvement of multiple myeloma. Plasma cell leukemia at the time of screening (>2.0×109 /L plasma cells by standard differential), Waldenström's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), or primary AL amyloidosis.

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
Interventional Model Description: GC012F will be administrated in one infusion
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GC012F<br>GC012F will be administrated in one infusion | Biological: GC012F<br>* GC012F is a BCMA/CD19 dual CAR product under investigation for the treatment of patients with RRMM.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1b Adverse Events (AEs) | The incidence and severity of adverse events (AEs) | 2 years | 
| Phase 1b Dose-limiting toxicities | The DLT evaluation period is defined as the first 28 days of Cycle 1 | 28 days | 
| Phase 2 Overall response rate (ORR) | Overall response rate (ORR) as defined by the International Myeloma Working Group (IMWG) | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1b Pharmacokinetic - AUC | Area under the curve of the GC012F level | 2 years | 
| Phase 1b Pharmacokinetic - Cmax | Maximum GC012F level | 2 years | 
| Phase 1b Pharmacokinetic - half-life | The elimination half-life of GC012F level | 2 years | 
| Phase 1b Pharmacokinetic - Tmax | Time to reach Maximum GC012F level | 2 years | 
| Phase 2: Adverse Events (AEs) | Further characterization of the safety of GC012F by measuring the incidence and severity of AEs | 2 years | 
| Phase 1b and 2: Overall Response Rate (ORR) | Overall response rate (ORR) is defined as the proportion of subjects who achieve a PR or better according to the IMWG criteria. | 2 years | 
| Phase 1b and 2: Duration of response (DOR) | Duration of response (DOR) will be calculated among responders from the date of initial documentation of a response to the date of first documented evidence of progressive disease, as defined in the IMWG criteria, or death due to any cause, whichever occurs first. | 2 years | 
| Phase 1b and 2: PFS | Progression-free survival (PFS) defined as the time from the date of the initial infusion of GC012F to the date of first documented disease progression, as defined in the IMWG criteria, or death due to any cause, whichever occurs first. | 2 years | 
| Phase 1b and 2: OS | Overall survival (OS) is measured from the date of the initial infusion of GC012F to the date of the subject's death. | 2 years |