Phase I/II SAVE trial: All-oral revumenib + decitabine/cedazuridine + venetoclax triplet for R/R AML

Results from the single-center, open-label, phase I/II SAVE trial (NCT05360160), evaluating the all-oral combination of revumenib + decitabine/cedazuridine + venetoclax in patients aged ≥12 years with relapsed/refractory (R/R) KMT2A-rearranged (KMT2Ar; n = 17), NPM1-mutated (NPM1m; n = 16), or NUP98-rearranged (NUP98r; n = 9) acute myeloid leukemia (AML), were published in the Journal of Clinical Oncology by Issa et al. The phase I primary endpoint was maximum tolerated dose (MTD) or recommended phase II dose (RP2D) of revumenib, and the phase II primary endpoint was composite complete remission (CRc) rate within five cycles.

Key data: In this pretreated population (median prior lines of therapy [LoT], 2), revumenib 160 mg twice daily was selected as the RP2D. The CRc rate was 71% (95% confidence interval [CI], 57.8–85.1), exceeding the prespecified ≥35% promising efficacy threshold, and the overall response rate (ORR) was 88%. Measurable residual disease (MRD) negativity was achieved in 68% of evaluable responders (n = 37) and in 80% of patients with CRc (n = 30), while 45% of patients proceeded to allogeneic hematopoietic stem cell transplantation (allo-HSCT). Overall, the 1-year overall survival (OS) rate was 56%. Emergent MEN1 mutations occurred in 13% of evaluable patients and were associated with relapse. Grade ≥3 treatment-emergent adverse events (TEAEs) included febrile neutropenia (36%), lung infection (21%), thrombocytopenia (21%), and increased aspartate aminotransferase/alanine aminotransferase (AST/ALT; 21%). Differentiation syndrome and QT interval prolongation occurred in 10% and 43% of patients, respectively, including 5% who experienced Grade ≥3 events, for both.

Key learning: This all-oral regimen showed clinically meaningful activity with a manageable safety profile in heavily pretreated patients with R/R KMT2Ar, NPM1m, or NUP98r AML, supporting further evaluation of this triplet regimen in this population.