Prexigebersen

Ohanian M, et al. Blood, 2021, 138, 1281.

Prexigebersen (BP1001) has emerged as a novel therapeutic agent targeting growth factor receptor-bound protein-2 (Grb2), a key mediator of acute myeloid leukemia (AML) progression. Grb2 inhibition disrupts downstream signaling pathways essential for AML cell survival and proliferation, making Prexigebersen a promising candidate for patients with high-risk and relapsed/refractory AML.
In a multi-center, open-label, Phase II study, Prexigebersen was combined with either decitabine (DAC) or DAC and venetoclax (VEN) to evaluate its safety and preliminary efficacy. High-risk AML patients unsuitable for intensive chemotherapy received BP1001 (60 mg/m² twice weekly for 8 doses per cycle) alongside DAC (20 mg/m² for 5 days) or DAC + VEN (400 mg daily).
Among six patients treated with BP1001 + DAC, two achieved complete remission with incomplete hematologic recovery (CRi), and one showed partial remission (PR). A second cohort receiving BP1001 + DAC + VEN exhibited higher response rates, with 67% achieving CR/CRi/morphologic leukemia-free state (MLFS) and 17% attaining PR. Median durations of therapy ranged from 140 to 177 days across cohorts.
Adverse events were consistent with AML and treatment regimens, including fatigue, diarrhea, and hematologic complications like febrile neutropenia and sepsis. These toxicities were generally manageable, affirming the safety of BP1001-based combinations.