Revumenib trial meets complete remission endpoint for acute leukemia subsets
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Revumenib conferred complete remission or complete remission with partial hematologic recovery in nearly one-quarter of patients with two acute leukemia subtypes, according to the agent’s manufacturer.
Topline data from the pivotal phase 2 AUGMENT-101 trial suggested an acceptable safety profile among individuals with advanced acute leukemias with KMT2A rearrangements who received revumenib (SNDX-5613, Syndax Pharmaceuticals) — an oral small-molecule menin inhibitor. FDA previously granted breakthrough therapy designation to the investigational therapy for treatment of adults and children with relapsed or refractory acute leukemias harboring a KMT2A rearrangement.
"There is a critical need for new therapies to treat [relapsed or refractory] KMT2Ar acute leukemias,” Ibrahim Aldoss, MD, associate professor in the division of leukemia, department of hematology and hematopoietic cell transplantation at City of Hope and principal investigator for the AUGMENT-101 trial, said in a Syndax-issued press release.
“There are no approved treatments for this population, where currently the expected response rate to standard of care treatment is less than 10%, and the expectation for survival is less than 3 months,” Aldoss added. “This pivotal dataset of revumenib monotherapy in heavily pretreated [relapsed or refractory] patients is very compelling in that it demonstrates significant clinical benefit that includes deep molecular remissions and is well tolerated.”
The open-label AUGMENT-101 trial enrolled 92 adult and pediatric patients with relapsed or refractory KMT2A-rearranged acute myeloid leukemia and acute lymphoid leukemia, 57 of whom comprised the available efficacy population for the study’s interim analysis.
The trial met its primary endpoint with a complete remission (CR) rate or a CR with partial hematologic recovery (CRh) rate of 23% (95% CI, 12.7-35.8) among those who received revumenib. Thirty-six of 57 patients responded to therapy, for an overall response rate of 63% (95% CI, 49.3-75.6).
The interim analysis further showed a 6.4-month (95% CI, 3.4 to not reached) median duration of response as of the study’s July 24, 2023, data cutoff date. Seven of 10 complete responders also achieved minimal residual disease negativity upon further analysis.
The manufacturer reported a 9% dose reduction rate and 6% treatment discontinuation rate during the study. The most frequently reported treatment-related adverse events included nausea (28%), differentiation syndrome (27%), and QTc prolongation (23%).
No grade 4 or grade 5 events occurred during the study.
Based on the positive topline results and the recommendation of its independent data monitoring committee, Syndax said it plans to stop further accrual into the KMT2A-rearrangment cohorts of the AUGMENT-101 trial. The manufacturer also said it plans to submit a new drug application to the FDA for revumenib to treat patients with advanced KMT2A-rearrangment acute leukemias by the end of this year.
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