FDA Grants Orphan Drug Designation to Investigational Bispecific in Myeloma
ISB 1442, which received orphan drug designation from the FDA, is currently under investigation in a first-in-human phase 1/2 trial as a treatment for patients with relapsed/refractory multiple myeloma.
The FDA has granted orphan drug designation to the bispecific antibody ISB 1442 for managing relapsed/ or refractory multiple myeloma, according to a press release from Ichnos Sciences.1
"Reported new cases are on the rise year over year, making the potential clinical applications for ISB 1442 more relevant than ever before," according to the manufacturers of ISB 1442.
ISB 1442 is a first-in-class 2+1 BEAT® bispecific antibody that targeted CD38 and CD47 and aids in the treatment of relapsed/refractory multiple myeloma. The BEAT® platform was designed to allow for the development of immune cell engagers.
ISB 1442 demonstrated anti-tumor activity across multiple preclinical in vitro and in vivo tumor models compared with daratumumab (Darzalex) and magrolimab as part of an oral presentation at the 2021 American Society of Hematology (ASH) Annual Meeting.2 Investigators shared additional preclinical data supporting potential applications of the agent in the management of acute myeloid leukemia and T-cell acute lymphoblastic leukemia at the 2022 ASH Annual Meeting.3
Investigators began administering ISB 1442 to patients as part of a first-in-human phase 1/2 study (NCT05427812) in Australia starting in September 2022. Treatment sites in the United States are expected to open for this study in the second quarter of 2023.
“Receiving orphan drug designation for ISB 1442 is an important milestone on Ichnos' journey to developing potentially curative therapies for patients with multiple myeloma,” Cyril Konto, MD, president and chief executive officer of Ichnos Sciences, said in the press release. “Reported new cases are on the rise year over year, making the potential clinical applications for ISB 1442 more relevant than ever before.”
ISB 1442 is a human bispecific antibody that targets CD38 and CD47 with potential stimulating, antineoplastic, phagocytosis-inducing activities.2 The agent binds to CD47, blocking the interaction between CD47 with SIRPalpha and thereby inhibiting CD47 and SIRPalpha-mediated signaling and inhibition of phagocytosis.
Investigators of the first-in-human, open-label phase 1/2 study (NCT05427812) are evaluating the safety and efficacy of ISB 1442 in patients with relapsed or refractory multiple myeloma. In phase 1, patients will receive ISB 1442 weekly by subcutaneous injection in each 28-day cycle followed by dose escalation with an accelerated titration dose escalation or a standard 3 plus 3 dose escalation if conversion criteria are fulfilled. Findings from phase 1 inform a recommended phase 2 dose for ISB 1442 injections as part of 28-day treatment cycles.
The primary end points of the trial include the frequency and severity of treatment-emergent adverse effects, dose-limiting toxicities, and overall response rate based on International Myeloma Working Group criteria. Secondary end points include time to progression, time to next treatment, time to response, progression-free survival, overall survival, complete response rate, and duration of response.
Patients 18 years or older with pathologically confirmed multiple myeloma that has progressed on or after standard therapy are eligible for enrollment on the trial. Additional eligibility criteria include having a body weight of 40 kg or higher at screening, an ECOG performance status of 2 or less, a life expectancy of at least 3 months, adequate organ function, and a left ventricular ejection fraction of at least 45% as assessed by echocardiogram or a multiple gated acquisition scan.
Patients with relapsed disease characterized only by minimal residual disease parameters or multiple myeloma with disease where the only measurable parameter is plasmacytoma are not eligible for enrollment. Patients are also unsuitable for enrollment if they have received prior treatment with anti-CD38 antibodies or CD47-targeting therapies within 1 month of beginning study treatment, received autologous stem cell transplantation within 12 weeks of beginning study treatment, active malignant central nervous system involvement, or are known to be refractory to platelet or red blood cell transfusions.
Investigators began administering ISB 1442 to patients as part of thea first-in-human phase 1/2 study (NCT05427812) in Australia starting in September 2022. Treatment sites in the United States are expected to open for this study in the second quarter of 2023.
References
- Ichnos Sciences receives orphan drug designation for first-in-class bispecific (CD38 x CD47) antibody innate cell modulator, ISB 1442. News release. Ichnos Sciences. March 21, 2023. Accessed March 28, 2023. prn.to/42PiyaM
- Stefano S, Grandclement C, Dehilly E, et al. ISB 1442, a first-in-class CD38 and CD47 bispecific antibody innate cell modulator for the treatment of relapsed refractory multiple myeloma. Blood. 2021;138(suppl 1):73. doi:10.1182/blood-2021-145586
- Stefano S, Grandclement C, Labanca V, et al. Preclinical evaluation of ISB 1442, a first-in-class CD38 and CD47 bispecific antibody innate cell modulator for the treatment of AML and T-ALL. Blood. 2022;140(suppl 1):6237-6238. doi:10.1182/blood-2022-162201
