Risk-stratified treatment of sonrotoclax with chemotherapy in newly diagnosed acute myeloid leukemia: a study protocol

Acute myeloid leukemia (AML) treatment relied on anthracyclines and cytarabine based intensive chemotherapy. However, clinical outcomes are unsatisfied for patients with intermediate/adverse cytogenetics based on European Leukemia Net (ELN) risk stratification 2022 (ELN 2022), and relapses also remain common even in patients with favorable-risk cytogenetics with measurable residual disease (MRD). There is an urgent unmet need for optimizing intensive chemotherapy regimens with novel agents, to enhance the MRD-negative rate, achieve durable remission, and improve the prognosis of AML. Preliminary results showed that adding a B-cell lymphoma-2 (BCL-2) inhibitor to intensive chemotherapy could improve treatment efficacy. Sonrotoclax is a potent, selective, next-generation BCL-2 inhibitor that effectively inhibits both the wide-type BCL-2 and several BCL-2 mutants. We hypothesize that the addition of sonrotoclax to intensive chemotherapy may enhance the treatment efficacy for AML without untoward toxicity. Here, we describe the rationale and design of a single-arm, multicenter, phase 2 study evaluating the efficacy and safety of sonrotoclax combined with chemotherapy as an induction therapy in newly diagnosed patients with AML who are fit for intensive chemotherapy, followed by stratified subsequent consolidation and maintenance treatment based on patients' ELN2022 at diagnosis and MRD results after induction.<b>Clinical Trail Registration</b>: NCT06497062.