IASO Biotherapeutics' Equecabtagene Autoleucel (Fucaso™) demonstrates promising results in treating relapsed/refractory multiple myeloma (R/RMM), according to data published in JAMA Oncology. The phase 1b/2 FUMANBA-1 study evaluated the efficacy and safety of this fully human anti-BCMA CAR-T therapy in patients who had previously received at least three lines of prior therapies.
The study included 103 patients who received Equecabtagene Autoleucel, with data assessed as of September 9, 2022, and a median follow-up of 13.8 months (range: 0.4-27.2 months). Among 101 evaluable patients, the overall response rate (ORR) was 96.0% (97/101), and the stringent complete response/complete response rate (sCR/CR) was 74.3% (75/101).
Efficacy and Durability
In patients without prior CAR-T therapy (n=89), the ORR was 98.9% (88/89), and the sCR/CR rate was 78.7% (70/89). The median time to response was 16 days (range: 11-179), and the 12-month progression-free survival (PFS) rate was 78.8% (95% CI: 68.6-86.0). Minimal residual disease (MRD) negativity was achieved by 95% (96/101) of the patients, with a median time to MRD negativity of 15 days (range: 14-186). All patients with sCR/CR achieved MRD negativity.
Updated data presented at the 2023 American Society of Hematology (ASH) Annual Meeting, with a median follow-up of 18.07 months, showed an ORR of 96.1% among 103 evaluable patients and an sCR/CR rate of 77.7%. In the subgroup without prior CAR-T therapy, the ORR reached 98.9%, with an sCR/CR rate of 82.4% and an MRD negativity rate of 97.8%. At 12 months post-infusion, 81.7% of these patients remained MRD-negative, with a 12-month PFS rate of 85.5%. Furthermore, Equecabtagene Autoleucel demonstrated prolonged persistence, with 50% of patients having a vector copy number (VCN) above the limit of detection at 12 months and 40% still having detectable VCN persistence at 24 months.
Safety Profile
The safety analysis revealed that 93.2% (96/103) of the patients experienced cytokine release syndrome (CRS), with most cases being grade 1 or 2. Only one patient experienced grade 3 or higher CRS. Immune effector cell-associated neurotoxicity syndrome (ICANS) developed in 1.9% (2/103) of the patients, with one case each of grade 1 and grade 2.
Expert Commentary
Professor Lu-gui Qiu noted the fully human scFv design addresses immunogenicity issues associated with animal-derived CAR-T cells, while maintaining optimal affinity for BCMA. Professor Huang He added that Equecabtagene Autoleucel has provided significant survival benefits to patients with R/RMM since its approval in China in June 2023.
Ongoing Research
IASO Bio is currently conducting a phase III clinical study (FUMANBA-3) of Equecabtagene Autoleucel for multiple myeloma patients who have received 1-2 lines of prior therapies. The company anticipates positive results from this study, potentially offering a new treatment option for a broader patient population.
