Primary Endpoint Met for Revumenib in Patients with AML and ALL

The novel drug, revumenib, led to a 23% complete remission (CR; disappearance of the disease) or complete response with a partial hematologic recovery (CRh; when specific blood cells have have returned to normal; CRh)) in patients with KMT2A-rearranged acute myeloid leukemia (AML) or acute lymphoid leukemia (ALL), meeting the primary goal of the AUGMENT-101 clinical trial, according to Syndax, Pharmaceuticals, the manufacturer of the drug.

In patients with KMT2A-rearranged AML, the response rate was at 24.5%. These results lasted for a longer period of time, with a median duration of about 6.4 months. Minimal residual disease (MRD; when there is a small number of cancer cells left in the body post-treatment) was observed within 10 patients who showed improved results within the study, and results showed that 70% showed no signs of MRD.

Throughout all the patients studied, the overall response rate (the percent of patients who have a partial or complete response to therapy) was 63%. Within this group, 39% of patients who responded underwent a hematopoietic stem cell transplant (HSCT), and eight of these patients hadn’t received a CR or CRh before the HSCT. Out of the 14 patients, seven received ongoing treatment with revumenib after undergoing HSCT. Three more patients from this study remain in a follow-up phase.

"We are thrilled to report positive results for revumenib in KMT2A(-rearranged) acute leukemia that demonstrate the utility of its practice-changing clinical profile and highlight revumenib's potential as a first- and best-in-class agent," Michael A. Metzger, chief executive officer of Syndax, said in a press release. "A Breakthrough Therapy Designation has enabled us to work closely with the FDA to submit an NDA by year-end. Enrollment in the mNPM1 cohort of AUGMENT-101 is also progressing well, and we are rapidly advancing that program to an anticipated filing following KMT2A(-rearranged).”

Ninety-four patients were enrolled in the AUGMENT-101 trial with KMT2A-rearranged acute leukemia: 56% of these patients had their leukemia return after trying other treatments, while 46% had undergone a stem cell transplant before enrolling in the trial, and 72% received Venclexta (venetocolax) before enrolling in the trial.

The most common side effects that led to dose reductions was low (9%) and 6% of patients stopped treatment overall. More than 20% of patients were affected by nausea (28%), differentiation syndrome (a type of severe response to anticancer drugs, 27%) and QTc prolongation (time between heart contracting and relaxing).

"There is a critical need for new therapies to treat (relapsed/refractory) KMT2A(-rearranged) acute leukemias. 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 three months. This pivotal dataset of revumenib monotherapy in heavily pretreated (relapsed/refractory) patients is very compelling in that it demonstrates significant clinical benefit that includes deep molecular remissions and is well tolerated," said Dr. Ibrahim Aldoss, assistant attending physician and associate professor, Division of Leukemia, Department of Hematology & Hematopoietic Cell Transplantation at the City of Hope, and principal investigator in the AUGMENT-101 trial.

"The responses were durable with a high proportion of patients proceeding to potentially curative transplant and re-starting revumenib therapy. This is especially impressive given that these patients would generally not have an option for transplant with the current treatment options."

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