ISB 2001, a trispecific T-cell engager targeting BCMA and CD38, showed expected immune activity and no dose-limiting toxicities in an ongoing phase 1 study in relapsed or refractory multiple myeloma (MM), according to a poster presented at the 2025 American Association for Cancer Research Annual Meeting.
In this AACR presentation, the researchers provided updates on the pharmacokinetics (PK) and pharmacodynamics (PD) results from the ongoing trial, which is evaluating the therapy in participants with relapsed/refractory MM.
The researchers reported in the poster that 21 patients received ISB 2001 across seven dose levels between 5 and 1,200 µg/kg. The overall response rate was 89.5% at effective dose levels, and 78% in patients previously treated with T-cell–directed therapy. Soluble BCMA and B-cell levels dropped quickly, with responses seen after the first cycle, the investigators reported in the poster abstract.
Pharmacokinetics were dose proportional with a half-life over 10 days. T-cell activation markers and cytokines spiked briefly. Only low-grade cytokine release syndrome was reported, with no ICANS, dose-limiting toxicities, or treatment-related deaths.
“ISB 2001… demonstrated dose proportional PK and a high ORR across a range of dose levels in patients with heavily pre-treated RRMM, including patients previously treated with T-cell-directed therapies,” the investigators wrote.
The investigators confirmed that the therapy was working as expected, noting that biomarker findings support its tumor-targeted activity and align with the mild to moderate immune-related side effects seen in the clinic.
Reference
Garton A, Menon V, Quach H. Pharmacokinetics (PK) and pharmacodynamics (PD) of ISB 2001, a novel BCMAxCD38xCD3 trispecific antibody from the first-in-human (FIH) phase 1 study in relapsed/refractory multiple myeloma patients. Abstract# CT147. Presented at the 2025 American Association for Cancer Research Annual Meeting; April 25-30; Chicago.
