Background: DSP-5336, a menin MLL interaction inhibitor, elicited antitumor activity in MLL–r or NPM1m acute leukemia models in vitro and in vivo. An open-label, single-arm, phase 1/2 study (NCT04988555) will evaluate the safety and efficacy of DSP-5336 and determine the recommended phase 2 dose (RP2D) in patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) or acute lymphocytic leukemia (ALL). Methods: Patients aged ≥18 y with R/R AML, ALL, or acute leukemia of ambiguous lineage after ≥1 line of standard therapy, ECOG PS 0–2, and adequate organ function are eligible. Patients will receive DSP-5336 twice daily for 28 d/cycle. In phase 1, there will be two parallel escalation cohorts: patients who do not receive concomitant azole antifungal medication and patients who receive antifungal azoles (ie, posaconazole, voriconazole, or fluconazole); 21–30 patients will be enrolled during phase 1 into multiple ascending dose levels. Dose escalation will use a Bayesian logistic regression model. Phase 2 will enroll two arms: R/R AML with MLL–r and R/R AML with NPM1m (10–20 patients/arm). Patients will be treated at the RP2D to evaluate clinical activity and safety. Clinical trial information: NCT04988555.

Definitions: AE, adverse event; CR, complete response; CRh, complete remission with partial hematologic recovery; CRi, complete remission with incomplete hematologic recovery; DLT, dose-limiting toxicity; DOR, duration of response; ECG, electrocardiogram; ECHO, echocardiogram; EFS, event-free survival; MLFS, morphologic leukemia-free state; MRD, minimal residual disease; OR, objective response; PE, physical examination; PR, partial response; RFS, relapse-free survival; SAE, serious AE; TEAE, treatment-emergent AE; TI, transfusion independence; TTR, time to response.