TY - JOUR
T1 - Parsaclisib, a potent and highly selective PI3Kd inhibitor, in patients with relapsed or refractory B-cell malignancies
AU - Forero-Torres, Andres
AU - Ramchandren, Radhakrishnan
AU - Yacoub, Abdulraheem
AU - Wertheim, Michael S.
AU - Edenfield, William J.
AU - Caimi, Paolo
AU - Gutierrez, Martin
AU - Akard, Luke
AU - Escobar, Carolina
AU - Call, Justin
AU - Persky, Daniel
AU - Iyer, Swaminathan
AU - DeMarini, Douglas J.
AU - Zhou, Li
AU - Chen, Xuejun
AU - Dawkins, Fitzroy
AU - Phillips, Tycel J.
N1 - Funding Information:
The authors thank the patients who participated in this study and the investigators and teams who conducted the study. The authors acknowledge the contributions of Steven Shi (Incyte Corporation), who provided statistical programming support. Medical writing assistance was provided by Karolina Rzeniewicz (Evidence Scientific Solutions Inc., Philadelphia, PA) and funded by Incyte Corporation.
Publisher Copyright:
© 2019 by The American Society of Hematology
PY - 2019/4/18
Y1 - 2019/4/18
N2 - This phase 1/2 study assessed parsaclisib (INCB050465), a next-generation, potent, and highly selective phosphatidylinositol 3-kinase d (PI3Kd) 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 5 9), pyrexia (n 5 4), hypotension (n 5 3), and sepsis (n 5 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). Parsaclisib has demonstrated antitumor activity in relapsed or refractory B-cell NHL with the potential for improved long-term patient outcomes. Phase 2 studies in relapsed or refractory B-cell NHL subtypes are ongoing.
AB - This phase 1/2 study assessed parsaclisib (INCB050465), a next-generation, potent, and highly selective phosphatidylinositol 3-kinase d (PI3Kd) 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 5 9), pyrexia (n 5 4), hypotension (n 5 3), and sepsis (n 5 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). Parsaclisib has demonstrated antitumor activity in relapsed or refractory B-cell NHL with the potential for improved long-term patient outcomes. Phase 2 studies in relapsed or refractory B-cell NHL subtypes are ongoing.
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U2 - 10.1182/blood-2018-08-867499
DO - 10.1182/blood-2018-08-867499
M3 - Article
C2 - 30803990
AN - SCOPUS:85065040619
SN - 0006-4971
VL - 133
SP - 1742
EP - 1752
JO - Blood
JF - Blood
IS - 16
ER -