In a phase I/II study (AUGMENT-101) reported in the Journal of Clinical Oncology, Issa et al found that revumenib, an oral small-molecule inhibitor of the menin-lysine methyltransferase 2A (KMT2A) interaction, was active in patients with KMT2A-rearranged (KMT2A) relapsed or refractory acute leukemia.
Study Details
In the trial, patients aged ≥ 30 days with relapsed or refractory KMT2A-rearranged acute leukemia (acute myeloid leukemia [AML], acute lymphocytic leukemia, or acute leukemia of ambiguous lineage) or with AML and an NPM1 mutation were enrolled from sites in five countries between October 2021 and July 2023. Patients received revumenib every 12 hours at 163 mg (95 mg/m2 if body weight was < 40 kg) with a strong cytochrome P450 inhibitor in 28-day cycles. The primary outcome measure was rate of complete remission or complete remission with partial hematologic recovery among patients with KMT2A-rearranged acute leukemia. The separate NPM1-mutant AML cohort is ongoing.
Key Findings
Among 57 patients evaluable for efficacy (median age = 34.0 years, range = 1.3–75.0 years), complete remission/complete remission with partial hematologic recovery occurred in 13 (22.8%, 95% confidence interval [CI] = 12.7%–35.8%), exceeding the protocol-defined null hypothesis of 10% (P = .0036). Median duration of complete remission/complete remission with partial hematologic recovery was 6.4 months (95% CI = 3.4 months to not reached).
The overall response rate (partial remission or better) was 63.2% (95% CI = 49.3%–75.6%), with 15 (68.2%) of 22 evaluable responders having no detectable residual disease. Median duration of partial remission or better was 4.3 months (range = 1.9 months to not reached).
Among 94 patients receiving treatment in the study, the most common adverse events of any grade were nausea (44.7%), febrile neutropenia (38.3%), diarrhea (35.1%), edema (31.9%), and vomiting (30.9%). The most common grade ≥ 3 adverse events included febrile neutropenia (37.2%), differentiation syndrome (16.0%), and QTc prolongation (13.8%). Adverse events led to treatment discontinuation in 12.8% of patients.
The investigators concluded, “Revumenib led to high remission rates with a predictable safety profile in relapsed/refractory [KMT2A-rearranged] acute leukemia. To our knowledge, this trial represents the largest evaluation of a targeted therapy for these patients.”
Eytan M. Stein, MD, of the Department of Pediatrics, Memorial Sloan Kettering Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Syndax Pharmaceuticals, Inc. For full disclosures of the study authors, visit ascopubs.org.
