Iaso Bio Presents at ASH 2024: Equecabtagene Autoleucel Demonstrates Significant Impact of CAR T-Cell Persistence on Clinical Outcomes in Relapsed/Refractory Multiple Myeloma

Dec 10, 2024 10:02 CST Updated 10:02

IASO Biotechnology

Cancer Treatment New Drug Developer

On December 10, 2024, IASO Bio presented a poster at the 66th American Society of Hematology (ASH) Annual Meeting in 2024, showcasing the impact of CAR-T cell persistence of its fully human BCMA-targeted CAR-T product, Equecabtagene Autoleucel Injection, on clinical outcomes in patients with relapsed/refractory multiple myeloma. The research findings confirmed thatThe effector-to-target ratio has a significant impact on the control of multiple myeloma, and further reveals that CAR-T therapy for multiple myeloma requires the selection of CAR-T drugs with long persistence of CAR-T cells, and their persistence is not affected by the baseline level of soluble B-cell maturation antigen (sBCMA).。

Report Title:Impact of CAR T-Cell Persistence on Clinical Outcomes in Relapsed/Refractory Multiple Myeloma: Insights from the Phase 2 FUMANMA-1 Study

Report No.:4761

Display Time:December 9, 2024, Monday, 6:00 PM - 8:00 PM (PST) / December 10, 2024, Tuesday, 10:00 AM - 12:00 PM (CST)

Research Conclusion

The efficacy-to-target ratio is a key determinant of clinical outcomes for patients treated with Icaritin injection, underscoring the importance of CAR-T cell persistence.

Effector-to-target ratio may become a biomarker for future treatment planning, emphasizing the necessity of prolonging CAR-T cell persistence for optimal disease control.

At the same time, the baseline sBCMA level of patients did not affect the persistence and efficacy of Icarusel.

This retrospective analysis of the FUMANBA-1 Phase 2 study primarily explores the relationship between CAR-T cell persistence and progression-free survival (PFS) as well as time to progression (TTP), and analyzes the impact of baseline soluble B-cell maturation antigen (sBCMA) levels from the perspective of the effector-to-target ratio, defined as the duration of vector copy number (VCN) to baseline sBCMA. With a median follow-up of 24.67 months, 107 subjects from 14 treatment centers received IASO Bio's Equecabtagene Autoleucel Injection.

At the data cutoff, the median VCN duration in the sustained response group tended to be longer than that in the progression or relapse group (12.52m vs 9.03m), as shown in Figure 1. The median efficacy-to-target ratio of the 107 subjects was 1.05 (day*mL/ng). As shown in Figure 2, subjects with lower efficacy-to-target ratios had a significantly higher risk of disease progression, with a hazard ratio (HR) for time to progression (TTP) of 3.07 (95% CI: 1.51–6.24, p=0.0011) and an HR for progression-free survival (PFS) of 2.3 (95% CI: 1.27–4.14, p=0.0045), both indicating a significant correlation between the efficacy-to-target ratio and the risk of disease progression.

Figure 1: Median VCN Duration (Months)

Figure 2: TTP Kaplan-Meier Curve

Swipe left or right to view more

Among baseline characteristics, including ECOG score, R-ISS and ISS disease staging, tumor BCMA expression, tumor burden, baseline sBCMA levels, prior autologous stem cell transplantation (ASCT), third-line treatment exposure, bridging therapy, prior CAR-T therapy, and lymphodepletion pretreatment, only prior autologous stem cell transplantation (n=30) and anti-drug antibodies (ADA, as a post-infusion factor) were significantly associated with the persistence of Icaroten-cel, with hazard ratios (HR) of 0.35 and 5.79, respectively, as shown in Table 1.

Table 1 Analysis of Factors Affecting CAR-T Cell Persistence

Among 107 subjects, only 14 exhibited neutrophil recovery障碍, characterized by neutrophil counts remaining below 500/μl for 14 days or longer. Compared with subjects without this manifestation, there was no significant difference in VCN duration, indicating that the long-term persistence of Icarus does not increase hematological toxicity.

This retrospective analysis explored the determinants of long-term efficacy following CAR-T treatment from the perspective of the efficacy-to-target ratio (VCN persistence/sBCMA), confirming the significant impact of the efficacy-to-target ratio on long-term myeloma control (PFS and TTP). It suggests that for CAR-T therapy in myeloma, products with prolonged efficacy, where efficacy is not influenced by target levels, should be selected—namely, CAR-T therapies with long persistence that are unaffected by sBCMA levels.

This study structure further reveals the important role of long-term persistence of CAR-T cells in improving the prognosis of subjects with relapsed/refractory multiple myeloma. In the 2023 ASH report, we have clearly confirmed a positive correlation between the persistence duration of CAR-T cells and the sustained state of minimal residual disease (MRD) negativity. The median persistence time of CAR-T cells with Equecabtagene Autoleucel reaches 419 days, which may be a key factor in achieving a high MRD negativity rate of 97.8% and an MRD negativity maintenance rate of 81.7% at 12 months.

Notably, among the 107 subjects in this study, only 14 developed neutropenia lasting more than 14 days, indicating that the long-term persistence of IASO Bio's therapy does not increase hematological toxicity, further validating the safety of this treatment.

Dr. Chen Jie

Chief Medical Officer of IASO Bio

The research data presented by IASO Bio during the ASH Annual Meeting emphasized the significant impact of effector-to-target ratio on the control of multiple myeloma. The data showed that patients with an effector-to-target ratio higher than the median had better prognoses for progression-free survival and time to disease progression. This finding further confirms the notably positive role of long-term CAR-T cell persistence in achieving sustained efficacy. In the early stages of development, the injectable Equecabtagene Autoleucel was meticulously designed to select a candidate molecule unaffected by sBCMA levels, providing trial participants with more pronounced and durable disease remission. Additionally, the study results indicated that only a small number of patients experienced neutropenia lasting over 14 days after treatment with Equecabtagene Autoleucel. This demonstrates that the long-term persistence of Equecabtagene Autoleucel does not increase hematological toxicity, further validating its safety.

We are highly confident in the significant efficacy and safety of the Icaritin injection. Currently, IASO Bio has initiated and is rapidly advancing a randomized controlled Phase 3 clinical trial for this therapy in second- and third-line multiple myeloma patients. We look forward to bringing this advanced treatment to a broader population of multiple myeloma patients both within and outside China as soon as possible.

About FUMANBA-1 Study

FUMANBA-1 is a single-arm, open-label Phase 1b/2 registrational clinical study conducted across 14 centers. It aims to evaluate the efficacy and safety of the fully human BCMA-targeted CAR-T cell therapy, Idecabtagene Vicleucel Injection, in patients with relapsed or refractory multiple myeloma (R/RMM) who have previously received three or more lines of therapy. Patients enrolled in this trial must have undergone at least three prior lines of therapy (including proteasome inhibitor and immunomodulatory agent-based chemotherapy regimens) and experienced progression on their last line of treatment. Subjects who have previously received BCMA CAR-T therapy are also eligible for enrollment.

About IASO Bio

IASO Bio is a biopharmaceutical company focused on the research, production, and commercialization of innovative cell-based drugs. With a foundation of innovation in developing cellular therapies and antibody drugs for hematological malignancies, the company has expanded its scope to autoimmune diseases, possessing comprehensive capabilities across the entire process from early discovery, clinical development, regulatory submission, to commercialization.

The company currently has more than 10 innovative drug candidates at various stages of development. Among them, the injection of Ixazomib (a fully human BCMA CAR-T product) has been approved for marketing by the National Medical Products Administration (NMPA) in China and has received permission from the U.S. FDA to conduct registration clinical trials for the treatment of relapsed/refractory multiple myeloma.

IASO Bio, with its strong management team, innovative product pipeline, self-owned GMP manufacturing, and robust clinical development capabilities, aims to provide transformative and curative innovative therapies, bringing hope of a cure to subjects in China and even globally.

For more information, please visit the company's official website: www.iasobio.com or LinkedIn account: www.linkedin.com/company/iasobiotherapeutics.