Clinical trial NCT05850234: A Study of GC012F (AZD0120), a CAR T Therapy Targeting CD19 and BCMA in Subjects With Relapsed/Refractory Multiple Myeloma
Official title: A Phase 1b/2 Study of GC012F (AZD0120), a Chimeric Antigen Receptor T-cell (CAR T) Therapy Targeting CD19 and B-cell Maturation Antigen (BCMA) in Subjects With Relapsed/Refractory Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Relapsed/ Refractory Multiple Myeloma
Keywords: Multiple Myeloma, BCMA, CAR
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2023-05-09
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: GC012F (AZD0120) will be administrated in one infusion
Primary purpose: TREATMENT

Brief summary: This trial is a phase 1b/2, open-label, multicenter study of GC012F (AZD0120), a CD19/BCMA dual CART-cell therapy, in adult subjects with relapsed/refractory Multiple Myeloma.

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 (AZD0120).

For Phase 2, it aims to evaluate the efficacy, to further characterize the safety of GC012F (AZD0120), 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Phase 1b Adverse Events (AEs)
timeFrame: 2 years
measure: Phase 1b Dose-limiting toxicities
timeFrame: 28 days
measure: Phase 2 Overall response rate (ORR)
timeFrame: 2 years
Secondary outcomes:
measure: Phase 1b Pharmacokinetic - AUC
timeFrame: 2 years
measure: Phase 1b Pharmacokinetic - Cmax
timeFrame: 2 years
measure: Phase 1b Pharmacokinetic - half-life
timeFrame: 2 years
measure: Phase 1b Pharmacokinetic - Tmax
timeFrame: 2 years
measure: Phase 2: Adverse Events (AEs)
timeFrame: 2 years
measure: Phase 1b and 2: Overall Response Rate (ORR)
timeFrame: 2 years
measure: Phase 1b and 2: MRD negative rate
timeFrame: 2 years
measure: Phase 1b and 2: Duration of response (DOR)
timeFrame: 2 years
measure: Phase 1b and 2: PFS
timeFrame: 2 years
measure: Phase 1b and 2: OS
timeFrame: 2 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Research Site
state: Alabama
city: Phoenix
country: United States
facility: Research Site
state: Arizona
city: La Jolla
country: United States
facility: Research Site
state: California
city: Los Angeles
country: United States
facility: Research Site
state: California
city: San Francisco
country: United States
facility: Research Site
state: California
city: Aurora
country: United States
facility: Research Site
state: Colorado
city: Denver
country: United States
facility: Research Site
state: Colorado
city: Jacksonville
country: United States
facility: Research Site
state: Florida
city: Miami
country: United States
facility: Research Site
state: Florida
city: Tampa
country: United States
facility: Research Site
state: Florida
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Iowa City
country: United States
facility: Research Site
state: Iowa
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Ann Arbor
country: United States
facility: Research Site
state: Michigan
city: Detroit
country: United States
facility: Research Site
state: Michigan
city: Minneapolis
country: United States
facility: Research Site
state: Minnesota
city: Rochester
country: United States
facility: Research Site
state: Minnesota
city: Omaha
country: United States
facility: Research Site
state: Nebraska
city: Hackensack
country: United States
facility: Research Site
state: New Jersey
city: Buffalo
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: Stony Brook
country: United States
facility: Research Site
state: New York
city: Charlotte
country: United States
facility: Research Site
state: North Carolina
city: Durham
country: United States
facility: Research Site
state: North Carolina
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: Austin
country: United States
facility: Research Site
state: Texas
city: Dallas
country: United States
facility: Research Site
state: Texas
city: Houston
country: United States
facility: Research Site
state: Texas
city: Salt Lake City
country: United States
facility: Research Site
state: Utah
city: Charlottesville
country: United States
facility: Research Site
state: Virginia
city: Edmonds
country: United States
facility: Research Site
state: Washington
city: Seattle
country: United States
facility: Research Site
state: Washington
city: Milwaukee
country: United States
facility: Research Site
state: Wisconsin
Study officials:
References: