Gracell’s BCMA/CD19 CAR-T GC012F Achieves 100% Stringent CR Rate in Newly Diagnosed Multiple Myeloma

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Notably, no patients experienced cases of immune effector cell-associated neurotoxicity syndrome.

Gracell Biotechnologies’ GC012F, an investigational autologous chimeric antigen receptor T-cell (CAR-T) therapy being evaluated for multiple indications, has demonstrated a 100% stringent complete response (sCR) rate in updated data from patients with newly diagnosed (ND) multiple myeloma (MM) treated in a phase 1 investigator-initiated clinical trial (NCT04935580).1

As of the August 1, 2023, data cut-off, all 19 patients (100%) who received GC012F in the trial had achieved an sCR with minimal residual disease negativity, with a sensitivity of 10-6 assessed by Euroflow. The patients’ follow-up ranged from 3.1 to 24.5 months (median, 15.3) and the median duration of response was not reached as of the cut-off. Gracell noted that the trial included patients with NDMM who were transplant eligible and that each of the patients, who were treated at 3 different dose levels (1x105 cells/kg, 2x105 cells/kg, and 3x105 cells/kg), had high-risk disease features. These included classification as stage II or stage III on the Revised International Staging System in 89% of patients and extramedullary plasmacytoma in 63% of patients.

In terms of safety, 5 patients experienced grade 1 cases of cytokine release syndrome (CRS) and 1 patient experienced a grade 2 case of CRS; no higher-grade CRS occurred. Notably, no patients experienced cases of immune effector cell-associated neurotoxicity syndrome.

GC012F targets both CD19 and B-cell maturation antigen (BCMA) and utilizes Gracell’s FasTCAR platform. FasTCAR allows for next-day manufacturing and is intended to limit the timespan for possible disease progression during manufacturing while reducing CAR-T production costs.2 Additional benefits noted by the company include potential for enhanced proliferation, tissue migration, lower dosage requirements, and antitumor activity because of the younger age of the CAR T-cells and better operational consistency and lower risk of contamination during manufacturing.

“Patients with high-risk NDMM, including those who are transplant-eligible, typically face suboptimal outcomes with the current standard of care,” Wendy Li, MD, the chief medical officer of Gracell, said in a statement.1 “Innovation is imperative to address the challenges faced by this group of hard-to-treat patients. MRD-negative sCR is the deepest response possible in the treatment of MM patients. We are delighted to report that in this study, all 19 NDMM patients treated by GC012F achieved MRD-negative sCR with favorable safety. This stands as a testament to the tremendous potential of CAR-T therapy, our pioneering BCMA/CD19 dual-targeting approach, and the enhanced T-cell fitness enabled by FasTCAR manufacturing technology.”

The day before announcing the updated data from this trial, Gracell shared that the first patient in the United States had been dosed in a separate phase 1b/2 clinical trial (NCT05850234) evaluating GC012F in patients with relapsed/refractory (r/r) MM.3 The company previously announced the FDA’s clearance of the investigational new drug application for this trial in February 2023.4 A separate phase 1/2 clinical trial in r/r MM in China is also planned for the CAR-T.1 In addition to NDMM and r/r/ MM, GC012F is also under investigation for the treatment of refractory systemic lupus erythematosus.

“Gracell has amassed a body of compelling evidence supporting the dual-targeting approach of GC012F for treatment of r/r MM,” William Cao, PhD, BM, the founder, chairman, and chief executive officer of Gracell, said in a September 26 statement.4 “Based on its fast, deep, and durable responses as well as the differentiated safety profile observed in prior clinical studies, we firmly believe that GC012F has the potential to emerge as a leading treatment option and benefit patients across disease stages. Dosing the first patient in the phase 1b portion of the US trial is another important step toward validating this treatment for r/r MM patients. We are grateful to everyone involved in this clinical study, including the investigators, clinical and manufacturing teams, and many others who collaborated seamlessly to expedite the prompt treatment of the first patient. Most of all, I’d like to thank the patients, and their loved ones, for participating in this trial.”

REFERENCES
1. Gracell Biotechnologies reports updated clinical data for FasTCAR-T GC012F for high-risk, newly diagnosed multiple myeloma, demonstrating 100% stringent complete response rate. News release. Gracell Biotechnologies Inc. September 27, 2023. Accessed October 2, 2023. https://ir.gracellbio.com/news-releases/news-release-details/gracell-biotechnologies-reports-updated-clinical-data-fastcar-t
2. FasTCAR. Gracell Biotechnologies Inc. Website. Accessed October 2, 2023. https://www.gracellbio.com/fastcar/
3. Gracell Biotechnologies doses first patient in phase 1b/2 clinical trial in U.S. evaluating GC012F for treatment of relapsed/refractory multiple myeloma. News release. Gracell Biotechnologies Inc. September 26, 2023. Accessed October 2, 2023. https://ir.gracellbio.com/news-releases/news-release-details/gracell-biotechnologies-doses-first-patient-phase-1b2-clinical
4. 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. Accessed October 2, 2023. https://ir.gracellbio.com/news-releases/news-release-details/gracell-biotechnologies-announces-fda-clearance-ind-application
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