A Study of Oral Nuvisertib (TP-3654) in Patients With Myelofibrosis

Patients must meet all of the following inclusion criteria to be eligible: Nuvisertib (TP-3654) Monotherapy Arm: * Confirmed pathological diagnosis of primary myelofibrosis (PMF) or post-PV-MF/post-ET- MF and intermediate or high-risk primary or secondary MF * Previously treated with JAK inhibitor(s) and is intolerant, resistant, refractory or has lost response to the JAK inhibitor(s) or is ineligible to be treated with JAK inhibitor * Fulfill the following clinical laboratory parameters: * Platelet count ≥ 25 x 10\^9 /L, without assistance of growth factors or platelet transfusions * ANC ≥ 1 x 10\^9/L without assistance of granulocyte growth factors * Peripheral blood blast count \< 5% * ECOG performance status ≤ 1 * Life expectancy ≥ 6 months * Adequate renal function * Adequate hepatic function * Adequate coagulation function * Splenomegaly (spleen volume of ≥ 450 cm3 by MRI or CT scan) within 2 weeks prior to Cycle 1 Day 1. * Dose escalation: At least 2 symptoms measurable (score ≥ 1) using the MF-SAF * Dose expansion: At least 2 symptoms measurable with each score of ≥ 3 or a total average score of ≥ 10 per MFSAF Nuvisertib (TP-3654) + Ruxolitinib Arm: * Confirmed pathological diagnosis of PMF or post-PV-MF/post ET- MF and intermediate or high-risk primary or secondary MF * On ruxolitinib treatment for ≥ 6 months, and on a stable dose of ruxolitinib (5 to 25 mg BID) for ≥ 8 weeks prior to the first dose of nuvisertib, but has either lost response or had a suboptimal …