Updated Results and Longer Follow-up from the AUGMENT-101 Phase 2 Study of Revumenib in All Patients with Relapsed or Refractory (R/R) KMT2Ar Acute Leukemia
Abstract
Background: Rearrangements of the lysine methyltransferase 2A (KMT2Ar) gene occur in ≤10% of acute leukemias (ALs) and are associated with a poor prognosis. In patients (pts) with KMT2Ar AL, the menin-KMT2A fusion protein interaction is a key driver of leukemogenesis. Revumenib, an oral, potent, and selective menin inhibitor, demonstrated a high rate of complete remission (CR) or CR with partial hematologic recovery (CR+CRh; 23%) and overall response rate (ORR; 63%) with a tolerable safety profile in pts with R/R KMT2Ar AL in the phase 2 interim analysis of AUGMENT-101 (NCT04065399). The KMT2Ar cohorts met prespecified stopping rules for efficacy, and the data from this analysis (n=57) were the basis for a New Drug Application to the FDA. Here we report longer follow-up and a larger data set, including safety and efficacy results for all pts with KMT2Ar enrolled in the phase 2 study (N=116), representing the largest evaluation of menin inhibition in pts with R/R KMT2Ar AL to date.
Methods: Pts aged ≥30 d with R/R KMT2Ar AL were enrolled and received revumenib 163 mg (95 mg/m2 if body weight <40 kg) every 12 h (q12h) with a strong CYP3A4 inhibitor azole in 28-d continuous cycles. Treatment continued until lack of at least morphological leukemia-free state (MLFS) after 4 cycles, disease progression, or unacceptable adverse events (AEs). Primary objectives were safety and tolerability and rate of CR+CRh. Key secondary endpoints included rate of composite CR (CRc [CR+CRh+CR with…
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