In a phase I/II study reported in The Lancet Oncology, Naval Daver, MD, and colleagues found that pivekimab sunirine (IMGN632), a novel CD123-targeting antibody-drug conjugate, showed activity in patients with CD123-positive relapsed or refractory acute myeloid leukemia (AML).
Naval Daver, MD
Study Details
Ninety-one patients from nine sites in France, Italy, Spain, and the United States were enrolled in the first-in-human study between December 2017 and May 2020. The dose-escalation phase examined dose levels of pivekimab sunirine given once every 3 weeks (schedule A; n = 68) or on days 1, 4, and 8 every 3 weeks (schedule B; n = 23).
Key Findings
No maximum tolerated dose was identified with pivekimab sunirine given at six escalating doses of 0.015 mg/kg to 0.450 mg/kg in schedule A. A total of three dose-limiting toxicities were identified, consisting of reversible veno-occlusive disease at 0.180 mg/kg and at 0.450 mg/kg and neutropenia at 0.300 mg/kg. Evaluation of schedule B was stopped on the basis of comparative safety and efficacy findings vs schedule A. The recommended phase II dose was 0.045 mg/kg once every 3 weeks (schedule A).
Among 29 patients receiving the recommended phase II dose, response defined as partial remission or better was observed in 6 patients (21%, 95% confidence interval [CI] = 8%–40%) and the composite complete remission rate (rate of complete remission or complete remission with partial or incomplete hematologic recovery) was 17% (95% CI = 6%–36%; n = 5). Among 68 patients receiving various doses in schedule A, response was observed in 11 patients (16%, 95% CI = 8%–27%) and the composite complete remission rate was 12% (95% CI = 5%–22%; n = 8).
Among 29 patients receiving the recommended phase II dose, the most common grade ≥ 3 treatment-related adverse events were febrile neutropenia (10%), infusion-related reactions (7%), and anemia (7%). The most common treatment-related serious adverse events were febrile neutropenia (7%) and infusion-related reactions (7%). Among the 68 patients receiving schedule A, death in one patient (due to unknown cause) was considered treatment-related.
The investigators concluded, “Pivekimab sunirine showed single-agent activity across multiple doses, with a recommended phase II dose of 0.045 mg/kg once every 3 weeks. These findings led to a phase Ib/II study of pivekimab sunirine plus azacitidine and venetoclax in patients with CD123-positive [AML].”
Dr. Daver, of The University of Texas MD Anderson Cancer Center, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by ImmunoGen. For full disclosures of the study authors, visit thelancet.com.
