Revumenib Shows Efficacy/Safety in Pediatric and Adult R/R KMT2Ar AML/ALL


Revumenib shows promise in treating both adults and children with specific types of leukemia, with similar safety and effectiveness.

White blood cells in leukemia, AI Generative: © Катерина Євтехова -

White blood cells in leukemia, AI Generative: © Катерина Євтехова -

Revumenib showed consistent safety and efficacy profiles across adult and pediatric patients with relapsed/refractory (R/R) KMT2A-rearranged (KMT2Ar) acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL), according to positive data from the pivotal AUGMENT-101 trial (NCT04065399).1

Fifty-seven patients were included in the efficacy-evaluable population, including 13 (23%) who were less than 18 years old. The median age of patients was 5 years, and each had central confirmation of their KMT2Ar status and sufficient follow-up. The pediatric patients enrolled were heavily pretreated with a median of 4 prior lines of therapy. This included 8 (62%) who were given prior treatment with venetoclax (Venclexta), 2 (15%) given prior chimeric antigen receptor T-cell therapy, and 6 (46%) that received prior hematopoietic stem cell transplant (HSCT).

Among the 13 pediatric patients, efficacy and safety data of the first-in-class Menin inhibitor in the phase 2 portion of the AUGMENT-101 study showed that the complete remission (CR) or CR with partial hematologic recovery (CRh) rate was 23% (95% CI, 5.0%-53.8%), and the median time to CR or CRh was 2.3 months (95% CI, 1.0-3.9). The overall response rate was 46% (n = 6), the composite response rate (CRc) was 39% (n = 5), and 60% of CRc patients achieved minimal residual disease-negative status. Further, the median overall survival was 6.9 months (95% CI, 2.3-not reached).

"We are pleased to present positive results from pediatric patients treated with revumenib in the AUGMENT-101 pivotal trial demonstrating impressive activity and consistency with the adult population," said Neil Gallagher, MD, PhD, president, head of research and development at Syndax, in the press release.

Of the 6 patients who achieved an overall response, 4 (67%) underwent HSCT. Two of these patients did not achieve a CR or CRh before transplant, and 2 of the patients who underwent HSCT were given posttransplant maintenance with revumenib. At the time of the July 24, 2023, data cutoff, these 2 were in remission for 6 and 9 months.

For safety, the agent was well-tolerated with a consistent safety profile to what has been reported prior. Grade 3 or greater treatment-related adverse events seen in more than 10% of patients were seen in 3 patients each and consisted of febrile neutropenia (13%) and decreased neutrophil count (13%). Investigators also observed grade 3 or greater differentiation syndrome in 2 patients (9%) and grade 3 QTc prolongation in 1 patient (4%).

There were no treatment-related discontinuations or dose reductions due to adverse events observed in the study.

"As the only Menin inhibitor with a formulation designed for the pediatric setting, we have an ongoing commitment to bringing this first- and best-in-class therapeutic agent to this important patient population in need of effective treatments," added Gallagher in the press release.

Background on Revumenib in Acute Leukemia

Revumenib is a first-in-class Menin inhibitor. Positive topline results from the phase 2 AUGMENT-101 trial showed that the trial met its primary end point with a CR/CRh rate of 23% (95% CI, 12.7%-35.8%; P =.0036).2,3

Additional data from the trial in this patient population were presented at the 2023 American Society of Hematology Annual Meeting, and data from the phase 1 portion of the AUGMENT-101 trial in acute leukemia were also published in Nature.2

In December 2022, the FDA granted a breakthrough therapy designation to revumenib for the treatment of adult and pediatric patients with R/R acute leukemia who harbor a KMT2A rearrangement.

Then in March 2024, the FDA granted priority review to the new drug application for revumenib in adult and pediatric relapsed or refractory KMT2A-rearranged acute leukemia and set a Prescription Drug User Fee Act target action date of September 26, 2024.

The new drug application filing for the agent is currently being reviewed under the FDA's real-time oncology review program, which allows for a more efficient review and engagement between the sponsor and the FDA throughout the submission process.

  1. Syndax presents positive pediatric data from pivotal AUGMENT-101 trial of revumenib in relapsed/refractory KMT2Ar acute leukemia at ASPHO plenary session. News release. Syndax Pharmaceuticals. April 8, 2024. Accessed April 8, 2024.
  2. Syndax announces FDA priority review of NDA for revumenib for the treatment of relapsed/refractory KMT2Ar acute leukemia. News release. Syndax Pharmaceuticals. March 26, 2024. Accessed April 8, 2024.
  3. Aldoss I, Issa GC, Thirman M, et al. Revumenib monotherapy in patients with relapsed/refractory acute leukemia topline efficacy and safety results from the pivotal augment-101 phase 2 study. Blood. 2023;142(supple 2): LBA-5. doi:10.1182/blood-2023-192042

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