Dual-target CAR-T ‘very promising’ for advanced multiple myeloma
Click Here to Manage Email Alerts
CHICAGO — A single dose of an investigational chimeric antigen receptor T-cell therapy induced an objective response in nearly 90% of patients with relapsed or refractory multiple myeloma, phase 1 study results showed.
Data from the trial — presented at ASCO Annual Meeting — indicated the agent exhibited a manageable safety profile. Researchers reported few cases of high-grade cytokine release syndrome and no treatment-related neurotoxicity.
Background
GC012F (Gracell Biotechnologies) is an autologous, gene-edited, bispecific CAR-T that targets the B-cell maturation antigen (BCMA) and CD19 proteins on the surface of cancer cells.
The novel cell therapy — which previously received FDA’s orphan drug designation —is manufactured within 24 hours of apheresis using Gracell's proprietary FasT CAR platform.
Researchers chose to use a dual-targeting CAR-T manufactured in a day or less for this study population of patients with heavily pretreated multiple myeloma to reduce the chance of disease progression prior to CAR-T infusion, according to Juan Du, MD, PhD, of Changzheng Hospital in Shanghai, China.
“BCMA is universally expressed on malignant plasma cells and is a well-established target for multiple myeloma, whereas CD19 is expressed on both myeloma cells and their progenitor cells,” Du said during a presentation. “GC012F is a second-generation BCMA and CD19 dual-targeting CAR-T that was designed to overcome antigen escape and to drive fast, deep and durable responses [among] patients with multiple myeloma.”
Methodology
Du and colleagues presented updated results on 28 patients (median age, 58 years; range, 27-76; 57% male) who received GC012F as part of a multicenter, first-in human dose-escalation study for patients with heavily pretreated relapsed or refractory multiple myeloma.
Study participants received a median five previous lines of therapy (range, 2-9), and 89% had what the investigators considered to be a “high-risk” disease profile.
Patients received lymphodepletion chemotherapy followed by a single infusion of GC012F at one of three dose levels — 1 ×105, 2 ×105 or 3 × 105 CAR T cells/kg).
Median follow-up was 6.3 months (range, 1.8-29.9), with a data cutoff date of Jan. 26.
Key findings
Twenty-five (89.3%) of 28 patients achieved objective responses to therapy after a single infusion of GC0-12F, including 21 (75%) with a minimal residual disease (MRD)-negative complete response or stringent complete response to therapy. Twenty-four (86%) patients had a very good partial response or better.
Median duration of response had not yet been reached.
All 27 patients with an evaluable MRD assessment achieved MRD negativity on at least one post-treatment bone marrow sample.
Safety results showed CRS to be the most common treatment-related adverse event. Grade 1 or grade 2 CRS occurred in 82% of patients. Researchers reported two cases of grade 3 CRS, and no grade 4 or higher cases.
Researchers reported no cases of treatment-related immune effector cell-associated neurotoxicity syndrome.
Clinical implications
Results thus far suggest the quick-turnaround platform that generates GC012F CAR T cells has produced a treatment with a favorable safety profile and high overall response rates, Du said.
“GC012F demonstrated fast, deep and durable response, with the longest ongoing response of over 29 months at date cutoff,” she said during the presentation. “Added together, GC012F dual-targeting CAR-T shows very promising activity in patients with relapsed or refractory multiple myeloma, including high-risk and heavily pretreated patients.”
Collapse
Du J, et al. Abstract 8005. Presented at: ASCO Annual Meeting; June 3-7, 2022; Chicago.
Read more about
Click Here to Manage Email Alerts