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Daiichi Sankyo Begins Phase I/II Trial of Menin Inhibitor in AML

NEW YORK – Daiichi Sankyo on Wednesday said it has dosed the first patient in a study exploring the activity of its menin inhibitor, DS-1594, in acute myeloid leukemia and acute lymphoblastic leukemia characterized by an MLL rearrangement or NPM1 mutation.

The Phase I/II trial is evaluating DS-1594 as a single agent and as part of combination regimens for patients with relapsed or refractory AML and ALL. Once the dose has been determined, the study will split patients into several cohorts. Some patients with AML and a MLL rearrangement or NPM1 mutation will receive just DS-1594, some AML patients will receive DS-1594 in combination with the chemotherapy azacitidine and venetoclax (AbbVie/Genentech's Venclexta), and patients with ALL with a MLL rearrangement will receive DS-1594 in combination with a mini-HCVD regimen, which includes low doses of cyclophosphamide, dexamethasone, methotrexate, and cytarabine.

The primary endpoints of the global Phase II part of the study include the rate of complete remission and complete remission with partial hematologic recovery in each AML cohort; the rate of complete remission with incomplete hematologic recovery for the ALL patients; and safety. The trial will enroll up to 170 participants and will initially be conducted at the MD Anderson Cancer Center, which has partnered with Daiichi Sankyo to develop AML treatments.

"Research has shown that the menin protein, which binds to MLL, plays a critical role in the development and growth of leukemias with MLL rearrangement," Arnaud Lesegretain, VP of oncology R&D at Daiichi Sankyo, said in a statement. "Our scientists designed DS-1594 to inhibit the menin-MLL interaction and disrupt the intracellular activity implicated in leukemogenesis. Together with MD Anderson, we will evaluate DS-1594 as a potential therapeutic option for patients with AML or ALL who have exhausted standard treatments."

MLL rearrangements occur in approximately 5 percent to 10 percent of acute leukemia patients, and NPM1 is mutated in about 30 percent of AML patients. Both mutations are associated with poor prognosis.