Abstract CT162: Addition of parsaclisib (INCB050465), a PI3Kδ inhibitor, in patients with suboptimal response to ruxolitinib: A phase 2 study in patients with myelofibrosis

Background: Ruxolitinib improves outcomes in patients (pts) with myelofibrosis (MF); however, suboptimal response may occur due to persistent PI3K/AKT pathway activation despite continued JAK inhibition. This phase 2 study (NCT02718300) evaluated optimal dosing and efficacy of add-on parsaclisib, a potent, highly selective next-generation PI3Kδ inhibitor, in pts with MF and suboptimal ruxolitinib response. Methods: Patients had primary/secondary MF, ECOG ≤2, and suboptimal response (palpable spleen >10 cm below left subcostal margin [LSM]; or palpable spleen 5-10 cm below LSM and active symptoms) after ≥6 months of ruxolitinib (5-25 mg BID; stable dose, ≥8 weeks [wks]). Patients remained on their stable ruxolitinib dose and were randomized to add-on parsaclisib QD/QW (10 or 20 mg QD for 8 wks/same dose QW thereafter) or parsaclisib QD (5 or 20 mg QD for 8 wks/5 mg QD thereafter). Endpoints: baseline-to-wk-12 spleen volume (SV) change by MRI/CT (primary endpoint); spleen length and symptom changes (Myelofibrosis-Symptoms Assessment Form Total Symptom Score [MFSAF-TSS]). Results: At data cutoff (1/20/2020), 33 pts received parsaclisib QD/QW; 20 received QD (median treatment duration, 197 days; median average daily doses: parsaclisib, 4.9 mg/day; ruxolitinib, 30.0 mg/day). Baseline median (range) SV (cm3) was 2333 (327-5324) in QD/QW (n=30) and 1890 (434-3741) in QD (n=17); median MFSAF-TSS was 10.8 (n=28) and 18.7 (n=17). In QD/QW and QD, median percent SV change was −2.3 (n=30) and −15.4 (n=17) at wk 12; and −2.5 (n=24) and −25.4 (n=9) at wk 24. In QD/QW and QD, number of pts with wk 12 SV reduction ≥10% were 10/30 (33%) and 10/17 (59%); ≥25% were 1/30 (3%) and 4/17 (24%); and ≥35% were 0 and 1/17 (6%). Median percent change in MFSAF-TSS at wk 12 was −14.0 (n=21) in QD/QW; −39.6 (n=12) in QD. Nonhematologic AEs were primarily grade 1/2. Grade 3/4 treatment-related, nonhematologic AEs included disseminated tuberculosis, enteritis, fatigue, hypertension, increased alanine aminotransferase, and increased aspartate aminotransferase in QD/QW and stomatitis in QD. In QD/QW and QD, 6/33 and 6/20 pts had new-onset grade 3 thrombocytopenia; 7/33 and 0/20 pts had grade 4 thrombocytopenia; hemoglobin levels remained steady during the study in both groups. Serious treatment-related AEs were stomatitis, herpes zoster infection, varicella zoster infection, and disseminated tuberculosis (each n=1). No colitis/dose-limiting diarrhea/rash occurred. In QD/QW and QD, 18/33 an