Context: Fedratinib is approved in the US for patients with Intermediate-2/High-risk myelofibrosis. Myelofibrosis can evolve from prior PV or essential thrombocythemia (ET). The ARD12042 study assessed fedratinib in patients with PV/ET. There was no response among 36 ET patients who received fedratinib 100-600 mg/day. Objective: Determine fedratinib clinical activity in patients with PV in ARD12042. Methods: Phase II, open-label, dose-ranging and -expansion study. Patients were aged ≥18 years with WHO-defined PV, ECOG-PS score ≤ 2, and were resistant/intolerant to hydroxyurea. Patients received once-daily fedratinib 100 mg, 200 mg, or 400 mg doses during the dose-ranging phase, and 400 mg during dose-expansion, in continuous 28-day cycles. All endpoints were prospectively defined. Response rate (RR) was the proportion of patients with hematocrit Results: 45 PV patients received fedratinib. Median age was 63 years (36-86) and 98% had ECOG-PS 0-1. The mITT population included 15 patients (13 dose-ranging, 2 dose-expansion): fedratinib 100 mg, n=2; 200 mg, n=5; 400 mg, n=8. RRs during dose-ranging were 0%, 40%, and 67% in the fedratinib 100 mg, 200 mg, and 400 mg groups. Both expansion phase patients responded. Clinicohematologic RRs were 20% and 63% with fedratinib 200 mg and 400 mg. Median SVRs from baseline at EOC8 were -16% and -39% in the 200-mg and 400-mg groups, respectively; 3 fedratinib 400 mg patients (38%) had ≥35% SVR. Among all patients, most common AEs were diarrhea (56%), nausea (53%), and vomiting (31%). Grade 3-4 AEs occurred in 21 patients (47%), most commonly lipase increases (11%) and abdominal pain (9%). Most frequent reason for treatment discontinuation was study termination (56%). AEs led to discontinuation for 7 patients (16%). Conclusion: Fedratinib 400 mg/day was manageable and induced hematocrit