CINC424H12201 (ADORE) (R/R)

A randomized, open-label, phase I/II open platform study evaluating safety and efficacy of novel ruxolitinib combinations in myelofibrosis patients

Study treatments

Ruxolitinib in combination with siremdalin or crizanlizumab or MBG453 (depending on open arm/cohort)

Inclusion criteria

• Subjects have diagnosis of PMF according to the 2016 WHO criteria, or diagnosis of ET, PET-MF, PV, PPVMF according to the IWG-MRT 2007 criteria
• Palpable spleen of at least 5 cm from the left costal margin to the point of greatest splenic protrusion or enlarged spleen volume of at least 450 cm3 per MRI or CT scan at baseline.
• Have been treated with ruxolitinib for at least 24 weeks prior to first dose of study treatment
• Are stable (no dose adjustments) on the prescribed ruxolitinib dose (between 5 and 25 mg twice a day) for ≥ 8 weeks prior to first dose of study treatment. 
• Hemoglobin < 10 g/dL - Part 1: Platelet counts ≥ 75 000/μL

Exclusion criteria

• Received any investigational agent for the treatment of MF (except ruxolitinib) within 30 days of first dose of study treatment or within 5 halflives of the study treatment, whichever is greater
• Peripheral blood blasts count of > 10%
• Received a monoclonal antibody or immunoglobulin-based agent within 1 year of screening, or has documented severe hypersensitivity reactions/immunogenicity (IG) to a prior biologic
• Splenic irradiation within 6 months prior to the first dose of study drug
• Received blood platelet transfusion within 28 days prior to first dose of study treatment.
• Subjects with known TP53 mutation or deletion of TP53

Participating sites

• University Hospital Leuven Gasthuisberg