A Phase 1 Study of AJ1-11095 in Patients With Primary Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (PPV-MF), or Post-Essential Thrombocythemia Myelofibrosis (PET-MF) Who Have Been Failed by a Type I JAK2 Inhibitor (JAK2i)

Inclusion Criteria

• 18 years of age or older.
• Diagnosis of PMF, post-PV MF, or post-ET MF.
• DIPSS Intermediate-2 or High-risk MF with ≤10% blasts, regardless of JAK2 mutation status.
• Estimated spleen volume ≥450cm3.
• MFSAF v.4.0 TSS ≥10, or at least 2 of 7 MFSAF-assessed symptoms with scores ≥3.
• ECOG PS of 0, 1, 2, or 3.
• Prior therapy with at least 1 type I JAK2 inhibitor, and either failed to achieve a response or relapsed after achieving a response.
• ANC ≥1.0×10^9/L.
• Platelet count ≥75×10^9/L.
• eGFR ≥45 mL/min/1.73m2.
• Serum total bilirubin ≤2.0 × upper limit of normal (ULN).
• AST and ALT ≤3.0 × ULN.
• QTcF ≤480 msec.

Exclusion Criteria

• Prior splenectomy.
• Splenic irradiation within 3 months prior to first dose of study drug.
• Ongoing use of systemic corticosteroids at dose equivalent to >10mg/day of prednisone.
• Uncontrolled intercurrent illness such as an acute infection.
• Chronic active or acute hepatitis B or C infection.
• Chemotherapy in the previous 4 weeks prior to first dose of study drug (Hydrea is permitted until 5 days before starting protocol therapy).
• Use of a Type I JAK2 inhibitor must have been discontinued for at least 5 days or 5 half-lives prior to dosing (whichever is longer).
• Use of erythropoiesis stimulating agents (unless stable for >8 weeks).
• Peripheral neuropathy ≥ Grade 2 (NCI CTCAE v 5.0).
• Unable or unwilling to undergo CT or MRI for spleen size imaging.
• Pregnant or breastfeeding.
• Requirement for therapy with a medication that is a strong CYP3A4 inhibitor as a concomitant medication.