研究 CDFV890G12101 是一项开放标签、第一期b、多中心研究，包含随机两剂量优化部分，以及由三个组别组成的剂量扩展部分，评估 DFV890 在髓系疾病患者中的应用。本研究旨在评估单药 DFV890 在较低风险（LR：极低、低或中等风险）骨髓增生异常综合症患者中的安全性、耐受性、药物动力学、药效学、疗效及推荐剂量。
适应症：Myeloid Diseases
入组条件
纳入标准
- \. 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.
- \. Patients must have one of the following for eligibility into the study:
- 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
- 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.
- changes for dose expansion (applicable as of amendment 3):
- 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.
- LR CMML patients with symptomatic cytopenias and/or constitutional symptoms refractory, intolerant or unsuitable for standard first-line therapy.
- 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.
排除标准
- \. 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.
- a. For TID LR MDS in Dose Expansion Phase only (applicable as of amendment 03):
- Prior therapy for MDS administered for \>4 months (ESA and luspatercept administered for ≤4 months will be allowed if washout period followed)
- Concurrent malignancy requiring active systemic therapy
- Prior or concurrent cytotoxic chemotherapy for MDS at any time
- \. History of hypersensitivity to the study treatment or its excipients or to drugs of similar chemical classes.
- \. 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)).
- \. 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.
- \. Patients receiving:
- a. concomitant medications that are known to be modulators of cytochrome P450 enzymes CYP2C9 and/or CYP3A (specifically strong or moderate inducers of CYP2C9, strong inducers of CYP3A enzymes, strong inhibitors of CYP2C9 and/or strong or moderate dual inhibitors of CYP2C9/CYP3A); and b. patients, who are poor CYP2C9 metabolizers receiving concomitant medications known to be strong or moderate inhibitors of CYP3A, whose concomitant medications cannot be discontinued or switched to a different medication within 5 half-lives or 1 week (whichever is longer) prior to start of study treatment and for duration of the study. See Section 6.8 and list of prohibited drugs in Appendix 8 for more details.
- \. Dose expansion only: Poor CYP2C9 metabolizers defined as genotype of the CYP2C9 \*3/\*3 or CYP2C9 \*2/\*3 allele combinations are excluded.
入组条件维持 ClinicalTrials.gov 原始英文登记资料，实际入组资格以研究团队的正式评估与受试者知情同意书为准。资料来源：ClinicalTrials.gov，每两周自动更新，最后同步：2026年10月8日。