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2023-03-29T16:03:36.000Z

U.S. FDA grants orphan drug designation to ISB 1442 for the treatment of RRMM

Mar 29, 2023
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Learning objective: After reading this article, learners will be able to cite a new clinical development in relapsed/refractory MM

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The U.S. Food and Drug Administration (FDA) has granted orphan drug designation to ISB 1442, a first-in-class anti-CD38/anti-CD47 bispecific antibody, for the treatment of relapsed/refractory (R/R) multiple myeloma (MM).1

ISB 14422

ISB 1442 is a biparatopic bispecific antibody with two binding arms to target CD38 and CD47. The CD47 and signal-regulatory protein alpha (SIRPα) interaction is blocked by the anti-CD47 arm, whilst the anti-CD38 arm drives binding with tumor cells and through avidity-induced binding can further block adjacent CD47 receptors. ISB 1442 has an engineered fragment crystallizable region to increase antibody-dependent cell cytotoxicity, antibody-dependent cell phagocytosis, and complement-dependent cytotoxicity. The structure and mechanism of action of ISB 1442 are outlined in Figure 1.

Figure 1. Mechanism of action of ISB 1442 mediated phagocytosis of tumor cells* 

FcyRs, Fc receptors for IgG; SIRPα, signal regulatory protein α.
*Adapted from Jiang.2 Created with BioRender.com.

Preclinical data2

In comparison with daratumumab, an anti-CD38 monoclonal antibody, ISB 1442 demonstrated increased antitumor potency in both high and low-CD38-expressing tumors. ISB 1442 showed increased on-target tumor impacts as well as no detectable red blood cell depletion in vitro compared with magrolimab in preclinical trials.

Clinical development

An open-label, first-in-human, multicenter phase I/II study (NCT05427812) will assess the safety, tolerability, efficacy, pharmacokinetics, and pharmacodynamics of ISB 1442 for R/R MM.3 Eligibility criteria include patients with R/R MM who have been treated with a CD38 antibody and have relapsed to three or more prior lines of therapy in the US.3

In this phase I trial, patients will be treated at escalating doses of ISB 1442 to establish its safety profile based on predetermined treatment-related adverse events.2 The phase II part of the trial, or dose expansion, will operate in two arms: the first being patients with three prior lines of therapy, including anti-CD38, and the second being patients who have received T cell-redirected therapies.2 The phase II primary endpoint is overall response rate. Secondary endpoints include progression-free survival, overall survival, duration of response, pharmacokinetics, and immunogenicity.2

  1. Ichnos Sciences receives orphan drug designation for first-in-class bispecific (CD38 x CD47) antibody innate cell modulator, ISB 1442. https://ichnossciences.com/ichnos-sciences-receives-orphan-drug-designation-for-first-in-class-bispecific-cd38-x-cd47-antibody-innate-cell-modulator-isb-1442/. Published Mar 21, 2023. Accessed Mar 23, 2023.
  2. Jiang T. A phase I/II, first-in-human, multicenter, open-label, dose-escalation and dose-expansion study of single-agent ISB 1442 in patients with relapsed/refractory multiple myeloma. Poster #4571. 64th American Society of Hematology Annual Meeting and Exposition; Dec 12, 2022; New Orleans, US.
  3. ClinicalTrials.gov. Phase I/II study of ISB 1442 in relapsed/refractory multiple myeloma. https://clinicaltrials.gov/ct2/show/NCT05427812. Updated Oct 17, 2022. Accessed Mar 23, 2023.

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