C051 | PRELIMINARY EFFICACY AND SAFETY OF LUSPATERCEPT (LUSPA) INITIATED AT THE MAXIMUM APPROVED DOSE IN TRANSFUSION-DEPENDENT LOWER-RISK MYELODYSPLASTIC SYNDROMES IN THE MAXILUS STUDY

BACKGROUND: LUSPA improved red blood cell transfusion independence (RBC-TI) in patients (pts) with TD LR-MDS in the COMMANDS and MEDALIST studies, with most pts titrating to the maximum dose. We report preliminary efficacy and safety from the phase 3b MAXILUS study (NCT06045689) where pts with TD LR-MDS initiated LUSPA at the maximum approved dose. METHODS: Eligible pts (≥18 yrs; had LR-MDS; were TD [required ≥1 unit packed RBCs ≤8 wks of first LUSPA dose]). Pts (cohort 1: erythropoiesis-stimulating agent [ESA]-naive; cohort 2: ESA-relapsed/refractory or intolerant [ESA-R/R/I]) received 1.75 mg/kg LUSPA SC Q3W. RBC-TI was evaluated Wks 1-24. Primary endpoint was RBC-TI ≥8 wks with concurrent mean hemoglobin (Hb) increase ≥1.0 g/dL. Secondary endpoints included RBC-TI ≥8 wks/≥12 wks and safety. RESULTS: At cutoff (Jan 15, 2025), 90 pts (ESA-naive, n=40; ESA-R/R/I, n=50) had received ≥1 dose. Among pts with first treatment (tx) ≥24 wks prior to cutoff (ESA-naive, n=17; ESA-R/R/I, n=33), the primary endpoint was achieved in 76.5% (ESA-naive) and 66.7% (ESA-R/R/I) of pts (Figure). RBC-TI ≥8 wks was reached in 76.5% (ESA-naive) and 69.7% (ESA-R/R/I) of pts, and RBC-TI ≥12 wks was reached in 70.6% and 42.4%. Among treated pts, 95.0% (ESA-naive) and 74.0% (ESA-R/R/I) were on tx at cutoff. Median (range) tx duration was 20.6 (1-37) wks (ESA-naive) and 23.9 (3-60) wks (ESA-R/R/I). Primary reasons for tx discontinuation were lack of efficacy (ESA-naive, 2.5%; ESA-R/R/I, 10%) and withdrawal (2.5%; 6.0%). ≥1 dose reduction occurred in 5.0% (ESA-naive) and 10.0% (ESA-R/R/I) of pts; 17.5% and 26.0% had dose delays. Primary reasons for dose adjustments were AEs (ESA-naive, 2.5%; ESA-R/R/I, 2.0%) and Hb increase >2.0 g/dL (0; 4.0%). TEAEs occurred in 72.5% (ESA-naive) and 84.0% (ESA-R/R/I) of pts. Serious TEAEs occurred in 22.5% (ESA-naive) and 30.0% (ESA-R/R/I) of pts. Grade 3/4 TEAEs occurred in 37.5% (ESA-naive) and 42.0% (ESA-R/R/I) of pts; 2.5% and 6.0% were related. TEAEs leading to drug interruptions occurred in 5.0% (ESA-naive) and 16.0% (ESA-R/R/I) of pts; dose reductions in 2.5% and 2.0%; and study intervention discontinuation in 0% and 2.0%. CONCLUSIONS: Initiating LUSPA at the maximum approved dose (1.75 mg/kg) was well tolerated, with low discontinuation rates and promising efficacy in both cohorts. Preliminary data suggest that this dosing had no new safety signals and may help pts with frontline and previously treated MDS achieve or maintain optimal responses.