A 2-Part, Phase 2, Open-Label Study of the Safety, Tolerability, and Efficacy of Itacitinib Immediate Release in Participants With Primary Myelofibrosis or Secondary Myelofibrosis (Post-Polycythemia Vera Myelofibrosis or Post-Essential Thrombocythemia Myelofibrosis) Who Have Received Prior Ruxolitinib and/or Fedratinib Monotherapy

INCB 39110-213/LIMBER-213

This is a 2-part study. In Part 1, participants will be dosed at 2 different dose levels in order to select the RP2D for Part 2 of the study.

2021-07-12

2023-08-24

2023-08-24

Completed

Early phase I

4

Inclusion Criteria: * Diagnosis of primary MF meeting the 2016 WHO criteria for overt PMF or secondary MF (PPV-MF or PET-MF) meeting the 2008 IWG-MRT criteria. * At least Intermediate 1 risk MF according to the DIPSS. * Prior treatment with ruxolitinib and/or fedratinib monotherapy * Currently receiving ruxolitinib or fedratinib monotherapy for PMF or secondary MF. * Splenomegaly defined as palpable spleen at least 5 cm below the left costal margin or volume ≥ 450 cm3 on imaging assessed during screening. * Allogeneic stem cell transplant not planned. * Platelet is greater than or equal to 50 × 109/L at screening. * Ability to comprehend and willingness to sign a written ICF for the study. * Willingness to avoid pregnancy or fathering children. Exclusion Criteria: * Prior treatment with a JAK inhibitor other than ruxolitinib or fedratinib * Record of ≥ 10% myeloid blasts in the peripheral blood (on peripheral blood smear) or bone marrow prior to or at the time of screening * For participants on ruxolitinib or fedratinib, unable to be tapered from that treatment over the course of 14 days without corticosteroids, hydroxyurea, or other agents * Treatment with ruxolitinib, fedratinib or other MF-directed therapy (approved or investigational) within 2 weeks of Day 1 * Prior splenectomy or splenic irradiation within 6 months before receiving the first dose of itacitinib * Unable or unwilling to undergo serial MRI or CT scans for spleen volume measurement * Unable or unwilling to complete MFSAF v4.0 diary on a daily basis during the study * ECOG performance status ≥ 3 * Life expectancy less than 24 weeks * Not willing to receive RBC or platelet transfusions * Participants with laboratory values at screening outside of protocol defined ranges * Significant concurrent, uncontrolled medical condition * Participants with impaired cardiac function or clinically significant cardiac disease unless approved by medical monitor/sponsor * History or presence of an abnormal ECG that, in the investigator's opinion, is clinically meaningful * Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment. * Evidence of HBV or HCV infection or risk of reactivation * Known HIV infection.

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'NON_RANDOMIZED', 'interventionModel': 'SEQUENTIAL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 4, 'type': 'ACTUAL'}}

2023-08-30