A phase 1/2, first-in-human, multicenter, open-label trial evaluating the safety, tolerability, and antileukemic activity of Debio 1562M in patients with recurrent refractory acute myeloid leukemia (AML)

Abstract Background and Significance: Acute Myeloid Leukemia (AML) is the most common adult acute leukemia and is an aggressive hematologic malignancy marked by abnormal proliferation of myeloid progenitor cells, often leading to poor outcomes and high relapse rates. Patients with relapsed or refractory (R/R) disease have dismal outcomes with complete remission (CR) rates of 5%-15% and median overall survival of 3 to 6 months with available therapies. CD37, also known as TSPAN26, is a trans-membrane protein member of the tetraspanin superfamily (Hemler 2005). In AML, increased CD37 expression on blasts and leukemic stem cells has been reported, at both protein and mRNA levels . This increased expression is restricted to malignant cells compared to hematopoietic stem cells and correlates with poor patient outcome . Moreover, expression is found across all subtypes of AML and MDS. Debio 1562M is an antibody-drug conjugate against CD37 that carries a peptidic cleavable linker (part of the Multilink™ linker technology) and a maytansinoid cytotoxic payload (DM1 derivative) at a drug-to-antibody ratio of 8. Study Design and Methods: This ongoing Phase 1/2 trial evaluates the safety and antileukemic activity of Debio 1562M in patients with relapsed or refractory acute myeloid leukemia (R/R AML) and R/R higher-risk myelodysplastic syndrome (HR MDS) (NCT06969430). The dose-escalation phase will explore different dose levels starting from 0.2 mg/kg, using an adaptive Bayesian logistic regression model with escalation and overdose control (BLRM-EWOC). The primary objective is to assess the safety and tolerability of Debio 1562M while determining doses for further evaluation in the subsequent dose-optimization phase. In the dose-optimization phase, participants will be randomized into two parallel arms in an open-label design. The primary objective is to identify the recommended dose (RD) for future clinical development. The phase 2 consists of an open-label single-arm study aimed at evaluating the antileukemic activity of Debio 1562M monotherapy at the RD in patients with R/R AML. Study results will provide insights into the clinical potential of Debio 1562M in patients with R/R AML for whom no standard therapy of proven benefit is available. Accrual is currently ongoing over several sites in United States of America and Europe.