Phase 1b Study of R289 in Patients with Lower-risk Myelodysplastic Syndromes (LR MDS)
Patient must be ≥ 18 years of age at the time of signing the informed consent.
Must have definitive diagnosis of MDS with very low, low, or intermediate-1 risk (International Prognostic Scoring System (IPSS)-R ≤ 3.5) and ≤5% bone marrow myeloblasts.
Must be relapsed, refractory/resistant, intolerant, or have inadequate response to therapies with known clinical benefits for MDS, such as EPOs, luspatercept, and HMAs(i.e., azacytidine or decitabine). Patients with del (5q) must have failed prior lenalidomide therapy.
Relapsed, refractory to or ineligible for ESAs and has previously received one or more approved therapies for LR-MDS
Prior treatment for MDS (i.e., TPOs, EPOs, luspatercept, HMAs) concluded < 4 weeks prior to study treatment
Clinically significant anemia resulting from iron, B12 or folate deficiencies, autoimmune or hereditary hemolysis, or GI bleeding.
MDS secondary to treatment with radiotherapy, chemotherapy, and/or immunotherapy for malignant or autoimmune diseases.
Diagnosis of chronic myelomonocytic leukemia.
Sequential
R906289 Monosodium (R289 Na)
DrugDrug: R906289 Monosodium (R289 Na) R906289 Monosodium (250mg PO qd, 250mg PO bid, 500 mg PO qd, 500 mg PO bid, 750 mg PO qd, split dose - 500 mg PO AM/250 mg PO PM)
Safety and Tolerability
* Incidence of adverse events (AEs) * Incidence of discontinuation or interruptions of R289 due to AEs * Incidence of dose limiting toxicities (DLTs)
Outcome Measure: Preliminary Efficacy
Measure Description Primary Efficacy: Proportion of patients achieving red blood cell transfusions independence by ≥ 8 weeks, ≥ 16 weeks, and ≥ 24 weeks Proportion of patients with overall response per IWG 2006 Proportion of patients with hematologic improvement per IWG 2018 Time Frame: 24 Weeks Measure Description Characterized PK Maximum plasma concentration (Cmax) Time Frame: 8 Weeks
Characterize pharmacokinetics (PK)
Maximum plasma concentration (Cmax)
Characterize pharmacodynamic (PD)
Change from baseline biomarker expression levels in plasma and bone marrow (including but not limited to, C-reactive protein \[CRP\] and tumor necrosis factor \[TNF\]-a)
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