Patrick Daly

Blood Cancers Today

Treatment with pivekimab sunirine (IMGN632), a first-in-class antibody drug conjugate (ADC) directed at CD123, showed single-agent activity across multiple doses in the treatment of patients with relapsed or refractory <a href="https://bloodcancerstoday.com/page/acute-myeloid-leukemia">acute myeloid leukemia</a> (AML), according to phase I/II trial data.
The authors of the <a href="https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(23)00674-5/abstract">study</a>, led by Naval Daver, MD, of the MD Anderson Cancer Center, identified a recommended phase II dose of 0.045 mg/kg once every three weeks.
Between December 2017 and May 2020, the study enrolled 91 patients to receive pivekimab sunirine in six doses escalating from 0.180 mg/kg to 0.450 mg/kg. The dose escalation phase evaluated a dosing schedule of once every three weeks on day one of a three-week cycle, as well as a fractionated schedule on days one, four, and eight of a three-week cycle. The fractionated schedule was discontinued after being compared with the normal schedule.
According to the report, no maximum tolerated dose was identified and three dose limiting toxicities were observed, including one case of reversible veno-occlusive disease each at doses of 0.180 mg/kg and 0.450 mg/kg, and one case of neutropenia at 0.300 mg/kg.
Among 29 patients treated at the recommended phase II dose, the overall response rate was 21% (n=6; 95% CI, 8-40) and the complete remission rate was 17% (95% CI, 6-36).
At the recommended phase II dose, the most common grade 3 or worse treatment-related adverse events (AEs) were febrile neutropenia (n=3), infusion-related reactions (n=2), and anemia (n=2). Treatment-related serious AEs in 5% or more of these patients were febrile neutropenia and infusion-related reactions in two each.
In closing, Dr. Daver and colleagues noted that these results prompted a phase Ib/II study of pivekimab sunirine combined with azacitidine and venetoclax in patients with CD123-positive AML.
Reference
Daver NG, Montesinos P, DeAngelo DJ, et al. Pivekimab sunirine (IMGN632), a novel CD123-targeting antibody-drug conjugate, in relapsed or refractory acute myeloid leukaemia: a phase 1/2 study. Lancet Oncol. 2024;25(3):388-399. doi:10.1016/S1470-2045(23)00674-5

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Pivekimab Sunirine Shows Promise For AML in Phase I/II Trial

The latest news, research, and perspectives in acute myeloid leukemia (AML). AML, an aggressive blood cancer, is the most common type of acute leukemia in adults and most often develops when myeloid cells that normally develop into the various types of mature blood cells instead form abnormal myeloblasts.

Acute Myeloid Leukemia

Pivekimab sunirine showed single-agent activity across multiple doses in the treatment of patients with relapsed or refractory acute myeloid leukemia.