AML-484 First Results of a Phase II Study (STIMULUS-AML1) Investigating Sabatolimab + Azacitidine + Venetoclax in Patients With Newly Diagnosed Acute Myeloid Leukemia (ND AML)

Although venetoclax+hypomethylating agent (HMA) therapy has improved outcomes for patients with ND AML who are unfit for intensive chemotherapy (IC), responses are often transient. Sabatolimab is a novel immuno-myeloid therapy targeting TIM-3. Sabatolimab+HMA has shown durable responses in a Phase Ib study in patients with ND-AML and myelodysplastic syndrome. Treatment with sabatolimab+venetoclax+azacitidine may also improve patient outcomes.To report findings from the dose-escalation part of STIMULUS-AML1 (NCT04150029) Design: Phase II, single-arm study Patients: Adult patients with ND-AML ineligible for IC Interventions: In the dose-escalation part (safety run-in), patients received either 400 mg (Cohort 1) or 800 mg (Cohort 2) sabatolimab every 4 weeks, 400 mg venetoclax once daily, and 75 mg/m2 azacitidine on Days (D) 1-7, or D1-5+D8-9, or D1-6+D8 of a 28-day cycle.Assessment of the incidence of dose-limiting toxicities (DLTs) between Cycle 1 D8 and the end of Cycle 2.As of September 6, 2021, 18 patients (median age, 77.0 years; males, n=13; ECOG PS 0-1, n=12), were treated with sabatolimab+azacitidine+venetoclax (Cohort 1, n=5; Cohort 2, n=13). Treatment was ongoing for 9 patients (Cohort 1, n=1; Cohort 2, n=8). Only 1 dose limiting toxicity (DLT) (elevated troponin T/asymptomatic myocarditis) was reported in Cohort 2. Treatment-related AEs (TRAEs) grade≥3 in >25% of all patients included neutropenia (39%), decreased platelet count (33%), and decreased neutrophil count (28%). TRAEs led to treatment discontinuation in 3 patients (platelet count decreased [n=2], troponin level increased/asymptomatic myocarditis [n=1]). AEs led to sabatolimab dose interruption in 6 patients in Cohort 2. No sabatolimab dosage reduction was observed. Fourteen patients experienced venetoclax dosage interruptions due to AEs and 5 patients had dosage reductions (none due to AEs). Serious AEs were reported in 14 (78%) patients; febrile neutropenia (44%) was the only event reported in >1 patient.Safety and tolerability of sabatolimab+azacitidine+venetoclax were comparable at 2 dose levels (400 and 800 mg) of sabatolimab and to the safety profile of venetoclax+azacitidine therapy. These findings supported initiation of the expansion cohort of STIMULUS-AML1 at a sabatolimab 800 mg dose.