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Official Title

A Phase 1b, Open Label, Multi-center, Dose Optimization and Dose Expansion Study to Assess the Safety and Efficacy of DFV890 in Adult Patients With Myeloid Diseases

Phase
Phase 1
Sponsor
Novartis Pharmaceuticals
Enrollment
105
Timeline
May 2023 → Feb 2027
About This Study

Study CDFV890G12101 is an open-label, phase 1b, multicenter study with a randomized two-dose optimization part, and a dose expansion part consisting of three groups evaluating DFV890 in patients with myeloid diseases. The purpose of this study is to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, efficacy and recommended dose for single agent DFV890 in patients with lower risk (LR: very low, low or intermediate risk) myelodysplastic syndromes (LR MDS), lower risk chronic myelomonocytic leukemia (LR CMML) and High-Risk Clonal Cytopenia of Undetermined Significance (HR CCUS).

Eligibility Criteria

Inclusion Criteria

  • 11\. 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.
  • 24\. Patients must have one of the following for eligibility into the study:
  • 3In 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
  • 4In 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.
  • 5changes for dose expansion (applicable as of amendment 3):
  • 6LR 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.
  • 7LR CMML patients with symptomatic cytopenias and/or constitutional symptoms refractory, intolerant or unsuitable for standard first-line therapy.
  • 8HR-CCUS: Diagnosis of high-risk CCUS by clonal hematopoiesis risk score (CHRS) with clinically meaningful cytopenias and no prior therapy for a myeloid neoplasm.

Exclusion Criteria

  • 11\. 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.
  • 2a. For TID LR MDS in Dose Expansion Phase only (applicable as of amendment 03):
  • 3Prior therapy for MDS administered for \>4 months (ESA and luspatercept administered for ≤4 months will be allowed if washout period followed)
  • 4Concurrent malignancy requiring active systemic therapy
  • 5Prior or concurrent cytotoxic chemotherapy for MDS at any time
  • 62\. History of hypersensitivity to the study treatment or its excipients or to drugs of similar chemical classes.
  • 73\. 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)).
  • 84\. 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.
  • 95\. Patients receiving:
  • 10a. 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.
  • 116\. Dose expansion only: Poor CYP2C9 metabolizers defined as genotype of the CYP2C9 \*3/\*3 or CYP2C9 \*2/\*3 allele combinations are excluded.

Locations

31 sites participating in this study

Emory University School of Medicine-Winship Cancer Institute

Atlanta, Georgia 30322

Recruiting

Nikolaos Papadantonakis

Stanford Cancer Center

Stanford, California 94305

Recruiting

Peter Greenberg

H Lee Moffitt Cancer Center and Research Institute

Tampa, Florida 33612

Recruiting

Zhuoer Xie

Data sourced from ClinicalTrials.govView on ClinicalTrials.gov →