Parsaclisib, a potent and highly selective PI3K{delta} inhibitor, in patients with relapsed or refractory B-cell malignancies

This phase 1/2 study assessed parsaclisib (INCB050465), a next-generation, potent, and highly selective phosphatidylinositol 3-kinase (PI3K) inhibitor, in patients with relapsed or refractory B-cell malignancies, alone or in combination with a Janus kinase 1 inhibitor (itacitinib) or chemotherapy (rituximab, ifosfamide, carboplatin, and etoposide). Seventy-two patients received parsaclisib monotherapy (5-45 mg once daily). Expansion doses were 20 and 30 mg once daily; intermittent dosing at 20 mg (once daily for 9 weeks, then once weekly) was explored. No dose-limiting toxicities were identified, and maximum tolerated dose was not reached. Most common nonhematologic treatment-emergent adverse events (TEAEs) were diarrhea/colitis (36%), nausea (36%), fatigue (31%), and rash (31%). Grade 3/4 neutropenia occurred in 19% of patients. Serious TEAEs (>2 patients) were diarrhea/colitis (n = 9), pyrexia (n = 4), hypotension (n = 3), and sepsis (n = 3). Aspartate and alanine transaminase elevations occurring before treatment discontinuation were grade 1, except 1 grade 3 event each, secondary to sepsis. Two patients experienced 3 fatal parsaclisib-unrelated TEAEs (respiratory failure; respiratory failure and sepsis). In non-Hodgkin lymphoma (NHL), objective response rates to monotherapy were 71% in follicular lymphoma, 78% in marginal zone lymphoma, 67% in mantle cell lymphoma, and 30% in diffuse large B-cell lymphoma; 93% of responses occurred at first assessment (~9 weeks). Parsa...

Source: Blood - April 17, 2019 Category: Hematology Authors: Forero-Torres, A., Ramchandren, R., Yacoub, A., Wertheim, M. S., Edenfield, W. J., Caimi, P., Gutierrez, M., Akard, L., Escobar, C., Call, J., Persky, D., Iyer, S., DeMarini, D. J., Zhou, L., Chen, X., Dawkins, F., Phillips, T. J. Tags: Lymphoid Neoplasia Source Type: research