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- Title
MDS-335: Ivosidenib (IVO) in Patients with IDH1-Mutant Relapsed/Refractory Myelodysplastic Syndrome (R/R MDS): Updated Enrollment for the MDS Sub-Study.
- Authors
DiNardo, Courtney D.; Foran, James M.; Watts, Justin M.; Stein, Eytan M.; de Botton, Stéphane; Fathi, Amir T.; Prince, Gabrielle T.; Stein, Anthony S.; Stone, Richard M.; Patel, Prapti A.; Roboz, Gail J.; Arellano, Martha L.; Erba, Harry P.; Pigneux, Arnaud; Stuart, Robert K.; Thomas, Xavier; Uy, Geoffrey L.; Lemieux, Ian R.; Zhang, Vickie; Kapsalis, Stephanie M.
- Abstract
Mutations in isocitrate dehydrogenase 1 (IDH1) occur in ~3% of patients with MDS and are associated with increased transformation to acute myeloid leukemia (AML). IVO is an oral, potent, targeted inhibitor of the mutant IDH1 (mIDH1) enzyme and is FDA-approved for m IDH1 R/R AML and m IDH1 newly diagnosed AML in patients ≥75 years old or with comorbidities precluding the use of intensive induction chemotherapy. In the first-in-human, phase 1 study of IVO in patients with m IDH1 advanced hematologic malignancies (NCT02074839), 12 patients with R/R MDS, with median age 72.5 years (range 52–78), received IVO 500 mg once daily (QD). All patients received prior MDS treatment. Investigator-assessed ORR (CR + PR + marrow CR, per IWG 2006) was 75% (95% CI 43–95), with median duration of response of 21.4 months (95% CI 2.3–NE). Nine (75%) patients were transfusion-independent for ≥56 days during treatment. No dose-limiting toxicities or adverse events leading to treatment discontinuation were reported among patients with MDS. Based on these encouraging data, the FDA granted Breakthrough Therapy Designation to IVO in m IDH1 MDS; the study was amended to enroll additional patients with m IDH1 R/R MDS. To evaluate safety, tolerability, clinical activity, and pharmacokinetics/pharmacodynamics of IVO in patients with m IDH1 R/R MDS. A sub-study of the single-arm, open-label, phase 1 dose escalation and expansion study of IVO in mIDH1 advanced hematologic malignancies, evaluating patients with R/R MDS. Patients must have R/R disease after prior standard therapy; high disease burden based on cytopenia and/or transfusion dependence at baseline; an Eastern Cooperative Oncology Group performance status score of 0–2; and be amenable to bone marrow aspirate and/or core biopsy at specified study timepoints. Patients with documented AML are not eligible. IVO 500 mg QD orally on days 1–28 of 28-day cycles. Study is open; enrollment of ~23 patients from the US and France planned. Results not yet available. This sub-study will provide additional insights into safety, tolerability, clinical activity, and pharmacokinetics/pharmacodynamics of treatment with IVO in patients with mIDH1 R/R MDS. Agios; Servier.
- Publication
Clinical Lymphoma, Myeloma & Leukemia, 2021, Vol 21, pS346
- ISSN
2152-2650
- Publication type
Article
- DOI
10.1016/S2152-2650(21)01805-X