FasTCAR-T Cells for High-Risk Myeloma

Dr. Juan Du presents a study that assessed the safety and feasibility of GC012F CAR-T therapy in the frontline setting for high-risk, transplant-eligible newly diagnosed multiple myeloma patients

Abstract title:

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

Purpose of the trial:

High-risk newly diagnosed multiple myeloma has poor outcomes with traditional first-line treatment, even for transplant-eligible patients. An effective and safe CAR-T therapy could address this unmet need. In a phase 1 study (GC012F), a dual-targeting CAR-T therapy targeting BCMA and CD19, produced by the FasTCAR-T platform, showed deep and lasting responses with a good safety profile in patients with relapsed or refractory multiple myeloma. The study assessed the safety and feasibility of GC012F CAR-T therapy in the frontline setting for high-risk, transplant-eligible newly diagnosed multiple myeloma patients.

Video summary:

As of July 25th 2022 data cutoff (the median follow-up 5.3 months, range 2.3-12.5 months), efficacy-evaluable pts (n= 13) was met, with 100% overall response rate (ORR) [95% confidence interval (CI), 72–100)]; 100% of pts (95% CI, 72-100) achieved very good partial response (VGPR) or better, with 69% (95% CI, 39–90) stringent complete response (sCR, Figure 1). 100% (4/4) of pts in DL 2 and 50% (4/8) of pts in DL3 achieved MRD negative-sCR after infusion, which might be the patients in DL2 group carried fewer HR factors than patients in DL3 group. All pts (100%) achieved minimal residual disease (MRD) negativity. There was no difference observed in dose levels. MRD assessment with Euroflow for landmark analysis at 1 month 1 and month 6 post infusion, 100% of evaluable pts were MRD negative at both timepoints. Cytokine release syndrome (CRS) occurred only in three pts (23%) with 15% grade 1 (n=2) and 8% grade 2 (n=1), respectively. There was no treatment-related grade ≥3 CRS and ICANS events. Robust CAR T-cell expansion occurred in all pts with a median time to Tmax of 10 days (range 9-14 d), and peak copy number (Cmax) of 63086 (20097-331159) copies /μg DNA.

Conclusions:

The phase I study for transplant-eligible, newly diagnosed high-risk multiple myeloma (MM) found the BCMA-CD19 dual FasTCAR-T therapy GC012F to have a very safe profile and high efficacy, with a 100% overall response rate and 100% negativity for minimal residual disease. The encouraging preliminary results suggest that GC012F should be further evaluated in a larger patient group with longer follow-up for transplant-eligible newly diagnosed MM.

Trial information:

ASH 2022: Abstract #366

Authors:

Juan Du, Weijun Fu, Jing Lu, Wanting Qiang, Haiyan He, Jin Liu, Ying Yang, Zhongyuan Feng, Lina Jin, Xiaoqiang Fan, Jia Liu, Qi Zhang, Lianjun Shen, Lihong Weng and Wei Cao