Rigel Pharmaceuticals has commenced a Phase Ib/II clinical trial to evaluate the efficacy and safety of REZLIDHIA (olutasidenib) in combination with decitabine and venetoclax for patients with acute myeloid leukemia (AML) harboring mutated isocitrate dehydrogenase-1 (mIDH1). The first patient has been enrolled in this multi-center, open-label, non-randomized study sponsored by The University of Texas MD Anderson Cancer Center.
The Phase Ib portion of the trial is designed to determine the safety, tolerability, and recommended Phase II dose of the combination therapy, involving oral or intravenous (IV) administration of decitabine and venetoclax along with olutasidenib in relapsed/refractory (R/R) mIDH1 AML patients. Following the Phase Ib stage, the Phase II portion will enroll 60 patients to primarily assess the complete remission rate in both newly diagnosed and R/R mIDH1 AML patients.
REZLIDHIA: A Targeted Approach
REZLIDHIA (olutasidenib) is an oral small-molecule inhibitor specifically targeting mIDH1. It functions by reducing the levels of 2-hydroxyglutarate, a metabolite elevated in mIDH1-mutated cancers, thereby promoting normal differentiation of myeloid cells. The drug is already approved for the treatment of R/R mIDH1 AML.
Strategic Alliance with MD Anderson
This clinical trial represents the first initiative under the multi-year strategic alliance between Rigel and MD Anderson. The collaboration aims to further investigate the potential of olutasidenib, both as a monotherapy and in combination with other agents, across a spectrum of hematologic neoplasms. This includes newly diagnosed and R/R AML, advanced myeloproliferative neoplasms (MPN), and higher-risk myelodysplastic syndromes (MDS).
Further studies will explore the use of olutasidenib as a single agent in conditions such as lower-risk MDS, clonal cytopenia of undetermined significance (CCUS), and as a maintenance treatment post-hematopoietic stem cell transplant.
Management Perspective
Raul Rodriguez, President and CEO of Rigel Pharmaceuticals, stated, "We believe REZLIDHIA has strong potential in a wide range of cancers where mIDH1 plays an important role. Studying REZLIDHIA in combination with two widely used agents in AML could provide a new all-oral front-line option to patients who are in urgent need of innovative treatments. MD Anderson is the ideal partner on this journey to evaluate REZLIDHIA’s impact on AML and other hematological cancers."
AML: An Unmet Need
Acute myeloid leukemia (AML) is an aggressive cancer affecting the blood and bone marrow. It is characterized by the rapid proliferation of abnormal myeloid cells. In the United States, approximately 20,800 new cases of AML are expected to be diagnosed in 2024, primarily in adults. Relapsed AML, occurring in about half of treated patients, and refractory AML, affecting 10-40% of newly diagnosed patients, highlight the urgent need for well-tolerated and effective treatments.
