Preclinical data support in-human studies of CD38 T-cell engager ISB 1342 for RRMM

ISB 1342 is a bispecific antibody that simultaneously targets CD38 and CD3 on multiple myeloma (MM) and T cells, respectively. Created using bispecific engagement by antibodies based on T-cell receptor (BEAT®) technology, ISB 1342 was designed to demonstrate low immunogenicity and binds to an alternative epitope on CD38 to daratumumab¹. Previously known as GBR 1342, the agent received orphan drug designation in 2019 for the treatment of relapsed/refractory MM (RRMM), in the hope to overcome resistance to daratumumab.

At the virtual 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, Marie-Agnès Doucey presented preclinical data surrounding ISB 1342 for the treatment of RRMM.¹ The topline findings from across the preclinical studies are summarized below:

• ISB 1342 demonstrated higher in vitro potency towards MM cells compared with daratumumab, irrespective of CD38 expression.
• Potency of ISB 1342 was sustained when applied in combination with daratumumab and soluble CD38 in MM cell models.
• The killing potential of ISB 1342 was not significantly impacted in vitro following addition of dexamethasone, suggesting that the agent could maintain potency if administered alongside glucocorticoids.
• CD38⁺ T-cell fratricide was not detected following treatment with ISB 1342, indicating high specificity for CD38⁺ MM cells.
• ISB 1342 exhibited higher in vivo potency compared with daratumumab, demonstrating full tumor control in mice xenograft models.
• ISB 1342 administration in mice MM xenograft models resulted in elevated levels of cytokines and immune effector molecules, such as granzyme A and B, TNF-α, and CXCL10 within the tumor microenvironment.

ISB 1342 represents a promising agent for the treatment of patients with RRMM, demonstrating encouraging in vitro potency and in vivo efficacy. Data from preclinical studies support the ongoing clinical evaluation of the T-cell engager: ISB 1342 is currently being evaluated in a phase I dose-escalation study (NCT03309111) in triple-class exposed/refractory patients,² which represent a current unmet medical need.