ISB 2001 Yields New Prospects as Multiple Myeloma Treatment

The first-in-human (FIH) phase 1 study of ISB 2001, a novel BCMA-targeting trispecific antibody, demonstrated both increased cytokine levels and increased expression of T-cell activation surface markers in patients with heavily pretreated relapsed or refractory multiple myeloma (MM).

The results were presented at the American Association for Cancer Research Annual Meeting 2025 by Andrew Garton of Ichnos Glenmark Innovation.

Patients responding to ISB 2001 demonstrated a rapid reduction in soluble BCMA levels within the first two treatment cycles, which were comparable in patients regardless of prior T-cell directed therapies. Expression of T-cell proteins (Ki-67 and HLA-DR) also increased in patients treated at effective dose levels of ISB 2001.

The phase 1 dose escalation trial included 21 patients treated across seven dose levels between 5 to 1200 μg/kg, with no dose-limiting toxicity observed. ISB 2001 was administered subcutaneously once per week in 28-day cycles. Step-up dosing was implemented on days 1 and 4, followed by full target dose starting on day 8.

The overall response rate was 89.5% (n=19) across the effective dose levels and 78% among the nine patients treated with prior T-cell directed therapy.

To monitor pharmacokinetics (PK) and pharmacodynamics profiles, the researchers assessed ISB 2001 serum concentrations, T-cell activation markers and serum concentrations of soluble biomarkers at several time points after treatment. Overall, ISB 2001 showed favorable dose proportional PK in patients with relapsed or refractory MM.

Optimized dosing of ISB 2001 was conducted to minimize cytokine release syndrome (CRS) and associated serum cytokine level changes. Grades 1 and 2 CRS occurred in 14 and two patients, respectively, following the first or second ISB 2001 doses. No immune effector cell-associated neurotoxicity syndrome, grade 5 adverse events (AEs), or AEs leading to treatment discontinuation were observed.

Overall, the study demonstrated clinical efficacy of ISB 2001 at target dose levels of 50 μg/kg and above. The next phase of study, focusing on dose expansion, will evaluate different putative doses and schedules.

Reference
American Association for Cancer Research Annual Meeting 2025. Abstract No. CT147.