GC012F CAR T Shows 100% Complete Response Rate in Multiple Myeloma

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Follow-up data from a continuing phase 1 trial evaluating a GC012F, an autologous dual-targeted CD19 and B-cell maturation (BCMA) chimeric antigen receptor (CAR) T-cell therapy identified it as a potential frontline treatment for patients with transplant-eligible, high-risk, newly diagnosed multiple myeloma (NDMM).¹

GC012F, manufactured by Gracell Biotechnologies, demonstrated a 100% overall response rate (ORR) and a 100% minimal residual disease stringent complete response (MRD-sCR) rate. The company presented its abstract at the 20th International Myeloma Society (IMS) Annual Meeting in Athens, Greece.

“MRD-sCR is the deepest response possible in the treatment of multiple myeloma patients,” said Dr. Wendy Li, chief medical officer at Gracell Biotechnologies. “This stands as a testament to the tremendous potential of CAR T-cell therapy, our pioneering BCMA/CD19 dual-targeting approach, and the enhanced T-cell fitness enabled by FasTCAR manufacturing technology.”

Early results from 16 patients in the study were presented at the 2022 American Society for Hematology (ASH) Annual Meeting.² An additional 3 patients were evaluated along with longer-term follow-up for the 16 initial patients. The open-label, single-arm, phase 1 investigator-initiated trial (IIT) treated patients with GC012F at 3 target dose levels. 89% of patients were classified as stage II or stage III, and 63% had extramedullary plasmacytoma. The 100% ORR and MRD-scR were achieved after a median follow-up time of 15.3 months (range, 3.1 months-24.5 months).

“Patients with high-risk NDMM, including those who are transplant-eligible, typically face suboptimal outcomes with the current standard of care,” said Dr. Li.¹ A high-risk characteristic like frailty shows a significantly shorter overall survival (OS)of 57% at 3 years than fit (OS 84% at 3 years) or unfit (76% at 3 years) patients.¹

The data showed that patients tolerated GC012F well, and no new safety signals were found. Six patients reported low-grade cytokine release syndrome (CRS). Of these cases, 5 cases (26%) were grade 1, and only 1 case was grade 2 (5%). No immune effector cell-associated toxicity (ICANS) of any grade was observed.

The 2 other FDA-approved CAR T-cell therapies for refractory or relapsed multiple myeloma cancer report higher occurrences of CRS. Ciltacabtagene autoleucel (Carvykti) reports that CRS occurred in 95% (92/97) of patients.³ Idecabtagene vicleucel (Abecma) reports CRS in 85% (108/127) of patients.⁴

In addition to the phase 1 study in patients with relapsed or refractory multiple myeloma, GC012F is being evaluated in patients with other hematological malignancies, including B-cell non-Hodgkin lymphoma.¹

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. Gracell Biotechnologies, Inc. Accessed September 27, 2023. https://tinyurl.com/4awv4akz

2. Du J, Fu W, Lu J, et al. Phaseiopen-label single-arm study ofbcma/cd19 dual-targetingfastcar-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

3. HIGHLIGHTS of PRESCRIBING INFORMATION. https://www.fda.gov/media/156560/download

4. Cytokine Release Syndrome | ABECMA® (idecabtagenevicleucel). www.abecmahcp.com. https://www.abecmahcp.com/safety#:~:text=Cytokine%20Release%20Syndrome%20(CRS)%2C