Revumenib Receives FDA Priority Review in R/R KMT2Ar Acute Leukemia

Supporting data for the NDA came from the phase 2 AUGMENT-101 trial (NCT04065399) assessing revumenib in patients with relapsed/refractory KMT2A-rearranged acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL).

The FDA has granted priority review to a new drug application (NDA) for the first-in-class menin inhibitor revumenib as a treatment for adult and pediatric patients with relapsed/refractory acute leukemia harboring KMT2A rearrangements, according to a press release from Syndax Pharmaceuticals, the developers of the agent.¹

The regulatory agency has assigned a Prescription Drug User Fee Act date of September 26, 2024, for its decision on approving revumenib in this population.

Supporting data for the NDA came from the phase 2 AUGMENT-101 trial (NCT04065399) assessing revumenib in patients with relapsed/refractory KMT2A-rearranged acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL). Investigators presented updated findings from this study at the 2023 American Society of Hematology (ASH) Annual Meeting and Exposition.

At the time of the protocol-defined interim analysis, 23% (n = 13/57; 95% CI, 12.7%-35.8%; P = .0036) of patients had a complete remission (CR) or CR with partial hematologic recovery (CRh).² Specifically, the CR or CRh rate was 23% (n = 10/44; 95% CI, 11.5%-37.8%) and 23% (n = 3/13; 95% CI, 5.0%-53.8%) in adult and pediatric patients, respectively. The median duration of CR/CRh was 6.4 months (95% CI, 3.4-not reached [NR]), and 46% (n = 6/13) of patients had ongoing responses as of the July 24, 2023, data cutoff.

The overall response rate (ORR) among efficacy-evaluable patients was 63% (n = 36/57; 95% CI, 49.3%-75.6%), and treatment yielded a composite response rate (CRc) of 44% (n = 25/57). Of those with evaluable minimal residual disease (MRD) status, MRD negativity was reported in 68% (n = 15/22). Additionally, the median overall survival (OS) was 8.0 months (95% CI, 4.1-10.9) as of the data cutoff.

Treatment-related adverse effects (TRAEs) resulted in dose reductions and treatment discontinuation for 9% (n = 8/94) and 6% (n = 6/94) of patients, respectively. Any-grade TRAEs included nausea (28%), differentiation syndrome (27%), and QTc prolongation (23%). Overall, investigators reported that the safety profile of revumenib in the AUGMENT-101 trial was comparable with prior reports of the agent.

“I am pleased that this pivotal dataset of revumenib as a monotherapy in heavily pretreated patients [with relapsed/refractory disease] continues to support its profile as a potential best- and first-in-class therapy,” principal investigator Ibrahim Aldoss, MD, an attending physician and associate Professor in the Division of Leukemia of the Department of Hematology & Hematopoietic Cell Transplantation at City of Hope, said in a press release on these findings.² “Responses were also observed across all major subgroups, with a similar CR/CRh rate across adult and pediatric patients, which speaks to the wide clinical utility of revumenib across this underserved patient population.”

In the phase 2 portion of the AUGMENT-101 trial, investigators assessed patients with relapsed/refractory NPM1-mutated AML, KMT2A-rearranged AML, and KMT2A-rearranged ALL. Enrollment is ongoing for patients with relapsed/refractory NPM1-mutated AML, the completion of which is anticipated early in the second quarter of 2024 at the latest. The trial’s primary end points include the CR/CRh rate, with DOR and OS as secondary end points.

The FDA previously granted breakthrough therapy designation to revumenib in KMT2A-rearranged acute leukemia in December 2022.³ Supporting data for the designation came from the AUGMENT-101 trial.

“The receipt of priority review for the revumenib NDA filing is a significant milestone as we transition to a leading commercial-stage oncology company with the planned launches of two first- and best-in class drugs in 2024," Michael A. Metzger, chief executive officer at Syndax Pharmaceuticals, said.¹

References

1. Syndax announces FDA priority review of NDA for revumenib for the treatment of relapsed/refractory KMT2Ar acute leukemia. News release. Syndax Pharmaceuticals Inc. March 26, 2024. Accessed March 27, 2024. https://tinyurl.com/s4uzvyaw
2. Syndax presents positive data from pivotal AUGMENT-101 trial of revumenib in relapsed/refractory KMT2Ar acute leukemia at late-breaking oral presentation during 65th ASH Annual Meeting. News release. Syndax Pharmaceuticals, Inc. December 12, 2023. Accessed March 27, 2024. https://tinyurl.com/3hxtj9zd
3. Syndax announces U.S. FDA breakthrough therapy designation granted for revumenib for the treatment of adult and pediatric patients with relapsed or refractory KMT2A- rearranged (MLLr) acute leukemia. News release. Syndax Pharmaceuticals, Inc. December 5, 2022. Accessed March 27, 2024. https://tinyurl.com/4b729u26