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

Relapsed/ Refractory Multiple Myeloma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05850234
• Other study ID #: GC012F-CD19/BCMA-001
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: July 20, 2023
• Est. completion date: June 2026

Study information

• Verified date: June 2024
• Source: Gracell Biopharmaceuticals, Inc.
• Contact: Grace Hong, MD
• Phone: 713-231-8670
• Email: grace.hong[@]gracellbio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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, to further characterize the safety of GC012F, 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 71
• Est. completion date: June 2026
• Est. primary completion date: March 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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, as defined by any of the following: serum monoclonal paraprotein (M-protein) =1.0g/dL (10 g/L); urine M-protein =200 mg/24 h; serum FLC assay: involved FLC level is =10 mg/dL (100 mg/L) and serum kappa lambda FLC ratio is abnormal.

• Adequate bone marrow and organ function assessment at screening according to the hematological, hepatic, and renal parameters listed in the CSP

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.

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell
• Relapsed/ Refractory Multiple Myeloma

Intervention

Biological:
• GC012F
GC012F is a BCMA/CD19 dual CAR product under investigation for the treatment of patients with RRMM.

Locations

Country	Name	City	State
United States	SAMC South Austin Medical Center	Austin	Texas
United States	Colorado Blood and Cancer Institute	Denver	Colorado
United States	Icahn School of Medicine at Mount Sinai	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Gracell Biopharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1b Adverse Events (AEs)	The incidence and severity of adverse events (AEs)	2 years
Primary	Phase 1b Dose-limiting toxicities	The DLT evaluation period is defined as the first 28 days of Cycle 1	28 days
Primary	Phase 2 Overall response rate (ORR)	Overall response rate (ORR) as defined by the International Myeloma Working Group (IMWG)	2 years
Secondary	Phase 1b Pharmacokinetic - AUC	Area under the curve of the GC012F level	2 years
Secondary	Phase 1b Pharmacokinetic - Cmax	Maximum GC012F level	2 years
Secondary	Phase 1b Pharmacokinetic - half-life	The elimination half-life of GC012F level	2 years
Secondary	Phase 1b Pharmacokinetic - Tmax	Time to reach Maximum GC012F level	2 years
Secondary	Phase 2: Adverse Events (AEs)	Further characterization of the safety of GC012F by measuring the incidence and severity of AEs	2 years
Secondary	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
Secondary	Phase 1b and 2: MRD negative rate	MRD negative rate asis defined by the IMWG response criteria	2 years
Secondary	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
Secondary	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
Secondary	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