Dual-Targeting, FasTCAR-T Therapy Cleared for Phase 1b/2 Trial in R/R Multiple Myeloma

GC012F recently showed efficacy in newly-diagnosed MM in investigator-initiated trials.

The FDA has cleared the investigational new drug application for Gracell Biotechnologies’ phase 1b/2 clinical trial of its FasTCAR-T chimeric antigen receptor (CAR) T-cell therapy, GC012F, in patients with relapsed/refractory multiple myeloma (R/R MM).1

"Advancing our lead therapeutic candidate into a U.S. clinical trial is major milestone for Gracell, and further validates our GC012F program, proprietary FasTCAR next-day manufacturing platform and novel dual-targeting approach," William (Wei) Cao, MD, PhD, founder, chairman, and chief executive officer, Gracell, said in a statement.1 "Having demonstrated deep responses and a favorable safety profile across indications, GC012F continues showing strong potential to become a transformative therapy. We look forward to initiating the Phase 1b/2 clinical trial and to bringing this promising therapeutic candidate one step closer to patients in need."

Gracell will initiate the phase 1b/2 clinical trial in the second quarter of 2023 in the US. The phase 1b portion will evaluate safety, tolerability, and pharmacokinetics of GC012F in patients with R/R MM as well as determine the recommended phase 2 dose. The phase 2 portion will evaluate efficacy, as well as further safety measures,

GC012F is an autologous CAR T-cell therapy developed with the use of Gracell’s proprietary FasTCAR platform. FasTCAR is designed to manufacture cells that appear younger and less exhausted, and has shown enhanced antitumor activity, proliferation, persistence, and migration in preclinical studies. The platform also boasts next-day manufacturing capabilities to improve efficiency and time-to-treatment.

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GC012F targets both CD19 and B cell maturation antigen (BCMA) and has received Orphan Drug Designation for treating R/R MM. It is currently being studied in multiple investigator-initiated trials in China in this indication as well as B-cell non-Hodgkin lymphoma.

Findings from an open-label phase 1 study of 16 transplant-eligible patients with newly diagnosed, high-risk R/R MM were presented at the 64th American Society of Hematology (ASH) Annual Meeting, held December 10-12, 2022, in New Orleans, Louisiana.2 These patients had an overall response rate (ORR) of 100% with all treated patients evaluable for minimal residual disease (MRD) showing MRD negativity to 12 months.

The patients were treated with GC012F as a single infusion at 1 of 3 dose levels: 1x105 cells/kg, 2x105 cells/kg, and 3x105 cells/kg. All patients showed robust CAR T-cell expansion with long persistence at all dose levels, and safety data demonstrated that only 4 patients (25%) experienced grade 1 or 2 cytokine release syndrome (CRS), all of which resolved within 4 days. There were no cases of grade 4 or 5 CRS.

“GC012F BCMA.CD19 dual-targeting CAR T-cell therapy shows very encouraging antitumor activity in transplant-eligible, high-risk, newly diagnosed multiple myeloma patients,” Juan Du, MD Shanghai Changzheng Hospital, The Second Military Medical University, China, said during his presentation of the data.2

1. Gracell Biotechnologies announces FDA clearance of the IND Application for phase 1b/2 clinical trial of FasTCAR-T GC012F for the treatment of relapsed/refractory multiple myeloma. News release. Gracell Biotechnologies. February 3, 2023. https://ir.gracellbio.com/news-releases/news-release-details/gracell-biotechnologies-announces-fda-clearance-ind-application
2. Du J, Fu W, Qiang W, et al. Phase I open-label single-arm study of BCMA/CD19 dual-targeting FasTCAR-T cells (GC012F) as first-line therapy for transplant-eligible newly diagnosed high-risk multiple myeloma. Blood. 2022;140(suppl 1):889-890. doi:10.1182/blood-2022-162295
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