Dose Optimization and Expansion Study of DFV890 in Adult Patients With Myeloid Diseases

Eligibility Criteria

• 1. Patients must be ≥ 18 years of age at the time of signing the informed consent form (ICF) 2. The Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2 3. Patient must be a candidate for serial bone marrow aspirate and/or biopsy according to the institutions guidelines and must be willing to undergo a bone marrow aspirate.
• 4. Patients must have one of the following for eligibility into the study:
• 1. In dose optimization: IPSS-R defined very low, low or intermediate risk Myelodysplastic Syndrome (LR MDS) who failed to respond to or did not tolerate ESAs or luspatercept or HMAs and patients with del 5q who failed to respond to or did not tolerate lenalidomide; or
• 2. In dose optimization and expansion: IPSS-R defined very low, low or intermediate risk Chronic Myelomonocytic Leukemia (LR CMML) who failed to respond to or did not tolerate hydroxyurea or HMAs.
• 3. changes for dose expansion (applicable as of amendment 3):
• 1. LR MDS with ≤ 10% bone marrow blasts, IPSS-R score of ≤ 3.5, transfusion independent (TID) status as per IWG 2006 criteria (requiring \<4U pRBC in 8 weeks), clinically meaningful cytopenia(s) and no or limited (\<4 months) prior therapy for MDS.
• 2. LR CMML patients with symptomatic cytopenias and/or constitutional symptoms refractory, intolerant or unsuitable for standard first-line therapy.
• 3. HR-CCUS: Diagnosis of high-risk CCUS by clonal hematopoiesis risk score (CHRS) with clinically meaningful cytopenias and no prior therapy for a myeloid neoplasm.
• 1. Systemic antineoplastic therapy (including cytotoxic chemotherapy, alpha-interferon, kinase inhibitors or other targeted small molecules, and toxin-immunoconjugates) or any experimental therapy within 28 days or 5 half-lives, whichever is longer, and recovered from the toxicities before the first dose of study treatment. For patients that received antibodies the washout period is 4 weeks prior to study treatment.
• 1. Prior therapy for MDS administered for \>4 months (ESA and luspatercept administered for ≤4 months will be allowed if washout period followed)
• 2. Concurrent malignancy requiring active systemic therapy
• 3. Prior or concurrent cytotoxic chemotherapy for MDS at any time
• 2. History of hypersensitivity to the study treatment or its excipients or to drugs of similar chemical classes.
• 3. Patients who have previously been treated with agents that have the same mechanism of action as DFV890 as defined in Table 6-7, list of prohibited medications (e.g., drugs targeting the NLRP3 inflammasome pathway and the IL-1 pathway (canakinumab and anakinra)).
• 4. Use of hematopoietic colony-stimulating growth factors (e.g., G-CSF, GM-CSF, M-CSF), thrombopoietin mimetics or erythroid stimulating agents anytime ≤ 1 week (or 5 half lives, whichever is longer) prior to start of study treatment.
• 5. Patients receiving:
• 6. Dose expansion only: Poor CYP2C9 metabolizers defined as genotype of the CYP2C9 \*3/\*3 or CYP2C9 \*2/\*3 allele combinations are excluded.