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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Relapsed/ Refractory Multiple Myeloma
• Intervention / Treatment: Biological: GC012F

Detailed 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, 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.

• Study Type: Interventional
• Enrollment (Estimated): 68
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Grace Hong, MD; Phone Number: 713-231-8670; Email: grace.hong@gracellbio.com

Study Locations

• United States
  • Colorado
    • Denver, Colorado, United States, 80218
      • Not yet recruiting
      • Colorado Blood and Cancer Institute
  • New York
    • New York, New York, United States, 10029
      • Recruiting
      • Icahn School of Medicine at Mount Sinai
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Not yet recruiting
      • SCRI Tennessee Oncology
  • Texas
    • Austin, Texas, United States, 78745
      • Not yet recruiting
      • SAMC South Austin Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Gracell Biopharmaceuticals, Inc.
• Investigators: Study Director: Yingda Wen, Gracell Biopharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): July 20, 2023
• Primary Completion (Estimated): March 1, 2026
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: April 18, 2023
• First Submitted That Met QC Criteria: April 28, 2023
• First Posted (Actual): May 9, 2023

Study Record Updates

• Last Update Posted (Actual): August 9, 2023
• Last Update Submitted That Met QC Criteria: August 7, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell
• Other Study ID Numbers: GC012F-CD19/BCMA-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No