Study Description
Study CDFV890G12101 is an open-label, phase 1b, multicenter study with a randomized
two-dose optimization part, and a dose expansion part consisting of two 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) and lower risk chronic myelomonocytic leukemia
(LR CMML). This research study is to find out if study treatment DFV890 is safe and tolerable, and
can help patients who were diagnosed with a myeloid disease such as: very low, low or
intermediate risk myelodysplastic syndromes (MDS) and very low, low or intermediate risk
chronic myelomonocytic leukemia (CMML). The study seeks to determine the optimal dose of
DFV890 that is safe and efficacious in patients with myeloid disease. The effectiveness
and safety/tolerability of the study treatment is not yet confirmed in this disease
setting.
Eligible patients meeting all study entry requirements will be required to provide a
sample from their bone marrow at screening and at select study timepoints. All enrolled
patients will be dosed for a minimum of twenty-four weeks (6 cycles of treatment) unless
they experience side effects related to the study treatment requiring dose
interruption/discontinuation, worsening of the disease, and/or if treatment is
discontinued at the discretion of the investigator or the patient.
Interventions
DFV890
Eligibility Criteria
Key Inclusion 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 and expansion: 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.
Key Exclusion Criteria:
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.
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 6-8, 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:
1. 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
2. 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.
Other protocol-defined inclusion/exclusion criteria may apply.
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