Autologous B Cell Maturation Antigen (BCMA) and CD19 Dual Targeting Fastcar-T Cells (GC012F/AZD0120) As First-Line Therapy for Elderly Patients with Newly Diagnosed Multiple Myeloma Patients

Background

Chimeric antigen receptor- (CAR) T cell therapy has dramatically improved outcomes in patients with relapsed/refractory multiple myeloma (RRMM) and is being evaluated in newly diagnosed multiple myeloma (NDMM) patients. Long-term follow-up from our previous trials (NCT04236011; NCT04182581; NCT04935580) strongly suggests that GC012F (AZD0120), a BCMA and CD19 dual-targeting CAR-T cell therapy developed using the novel FasTCAR-T platform, is effective in RRMM and high-risk transplant eligible NDMM patients aged <70 years. However chronological age can be a common reason for exclusion in a clinical trial setting. We thus performed a phase I single-arm study in elderly NDMM pts, age > 70 to characterize the safety and feasibility of GC012F CAR-T cell therapy (NCT05840107) in this patient population.

Methods

NDMM patients with measurable disease, age > 70, ECOG < 3 were eligible. After enrollment, patients were permitted to receive up to two cycles of bortezomib, lenalidomide and dexamethasone (VRd) induction therapy before or after apheresis, at the discretion of investigators. This was followed by standard flu/cy lymphodepletion and a single infusion of GC012F/AZD0120.

Nine patients were enrolled and apheresed. One patient withdrew due to disease progression before infusion. A total of 8 patients received GC012F/AZD0120 with a median age of 71.5 years, (range 70-78); 5 pts (62.5%) were male. Two pts (25.0%) were ISS stage II and 3 (37.5%) were ISS stage III. Three pts (37.5%) had 1q21 gain and two pts (25.0%) had 1q21 amplification.

All patients received two cycles induction therapy of VRd prior to infusion. GC012F/AZD0120 was administered as a single infusion at two dose levels of 1.5x10⁵/kg (n=3) or 3x10⁵/kg (n=5).

Results

As of the July 3^rd, 2024 data cut-off, median follow-up was 7.1 months (range 1.5-12.8 months). The overall response rate (ORR) and ≥ complete response (CR) rate were 100% and 62.5%, respectively. All treated pts (100%) achieved minimal residual disease (MRD) negativity assessed by Euroflow with a sensitivity of 10^-6. MRD negativity was achieved in 100%, of 8, 5, and 1 evaluable pts at Month 1, Month 6 and Month 12 respectively. Four pts (50%) experienced grade 1 cytokine release syndrome (CRS) with median time to onset of 9 days (range 6-18). All pts recovered from CRS within 5 days and only 1 pt received tocilizumab. No ICANS of any grade nor any cases of ≥grade 2 CRS were observed. Median duration of response (DOR) and progression-free survival (PFS) were not reached. Robust CAR T-cell expansion was observed in all pts; the median peak expansion (Cmax) was 96005.5 (range: 27177-285955) copies /μg DNA with a median Tmax of 10.5 days (range 9-28 d).

Conclusion

Consistent with the data from previous RRMM and transplant-eligible NDMM studies of GC012F, data from this study demonstrate that GC012F/AZD0120 resulted in a very favorable safety profile and promising, deep responses in elderly NDMM pts. Our results suggest that age alone should not preclude patients from receiving highly effective treatments aimed at cure or long-term disease control.

Shah:AstraZeneca: Current Employment, Current equity holder in publicly-traded company. Zhang:Gracell Biotechnologies Ltd., Shanghai: Current Employment. Liu:Gracell Biotechnologies Ltd., Shanghai: Current Employment. Weng:Gracell Biotechnologies Ltd., Shanghai: Current Employment. Shen:Gracell Biotechnologies Ltd., Shanghai: Current Employment. Cao:Gracell Biotechnologies Ltd., Shanghai: Current Employment.