ONGOING PHASE 1/2 STUDY OF INCB050465, A SELECTIVE PI3Kδ INHIBITOR, FOR THE TREATMENT OF PATIENTS (PTS) WITH RELAPSED/REFRACTORY (R/R) B‐CELL MALIGNANCIES (CITADEL‐101)

Abstract

Introduction: INCB050465 is a potent, selective PI3Kdelta inhibitor (>=19,000‐fold selectivity for PI3Kdelta vs other isoforms), which has demonstrated linear pharmacokinetics (PK) and achieved exposure levels several‐fold greater than the IC90 for PI3Kdelta inhibition at the recommended phase 2 dose (ASH 2016; Abstract 4195). Here, we report emerging safety and efficacy results from pts receiving INCB050465 monotherapy for r/r B‐cell malignancies in an ongoing phase 1/2 study (NCT02018861). Methods: Eligible pts (>=18 y) had ECOG PS =3 prior systemic regimens; 31% had prior HSCT. Median duration of therapy was 3.3 months (range, 0.6‐13.4); no DLTs were identified. Approximately 67% of pts discontinued therapy, most commonly for disease progression (31%) and AEs (25%). Approximately 33% of pts had dose interruption; 4% had reduction. Most common nonhematologic AEs (all grade [Gr]; Gr >=3) were nausea (38%; 0%), diarrhea (31%; 6%), and vomiting (25%; 0%). Gr >=3 hematologic AEs included neutropenia (21%), lymphopenia (17%), thrombocytopenia (10%), and anemia (4%). Approximately 40% of pts had serious AEs, most frequently colitis, diarrhea, and hypotension (all n = 3). A total of 1 pt had Gr 3 pneumonitis; none had Pneumocystis jiroveciipneumonia (PJP) or Gr >=2 elevated transaminase. Objective responses (OR) occurred at all doses (Table), except 5 mg QD; 90% of the ORs were observed at the 9‐week disease assessment. Conclusion: INCB050465 demonstrated manageable toxicities with no clinically meaningful transaminitis or PJP. OR rates were generally high and most responses (90%) were observed at the 9‐week disease assessment. Different dosing regimens/schedules, long‐term safety, and disease‐specific cohorts are being evaluated. (Table Presented).