FDA Grants BTD to Revumenib for Relapsed/Refractory KMT2Ar Acute Leukemia


Revumenib, which was given a breakthrough therapy designation by the FDA, may be beneficial in the management of relapsed or refractory KMT2A-rearranged acute leukemia based on data from the phase 1 AUGMENT-101 trial.

The FDA has granted breakthrough therapy designation to the oral menin inhibitor revumenib for the treatment of patients with relapsed or refractory acute leukemia harboring a KMT2A rearrangement, according to a press release from Syndax Pharmaceuticals.

The breakthrough therapy designation was supported by data from the phase 1 AUGMENT-101 trial (NCT04065399), additional data from which will be shared at the 2022 American Society of Hematology Annual Meeting & Exposition (ASH). In the study, 27% of patients (n = 10/37) with KMT2A-rearranged leukemia evaluable for efficacy achieved a complete remission (CR) as measured by a CR per partial hematologic recovery (CRh) after being treated with the recommend phase 2 dose. Investigators of the trial reported no treatment discontinuations due to treatment-related adverse effects.

“The breakthrough therapy designation underscores revumenib's potential as a first- and best-in-class therapy to meaningfully change the treatment paradigm for patients with [relapsed or refractory KMTA2-rearranged] acute leukemia, whether it presents clinically as acute myeloid leukemia or acute lymphocytic leukemia, in adults or children,” Michael A. Metzger, chief executive officer at Syndax, said in the press release. “Revumenib has the potential, if approved, to be the first drug to address the significant unmet need in KMT2A-rearranged leukemia believed to occur in up to 10% of all acute leukemias, including in approximately 80% of infant acute leukemias.”

In phase 1 of the AUGMENT-101 trial, investigators assigned patients to either arm A—226 mg and 276 mg of revumenib once every 12 hours without a strong CYP3A4 inhibitor—or Arm B—113 mg and 163 mg of revumenib once every 12 hours with a strong CYP3A4 inhibitor. Moreover, the study included several other arms: patients in arm C received revumenib and cobicistat; those in arm D received fluconazole (Diflucan) as an antifungal prophylaxis, arm E did not receive a CYP3A4 inhibitor of any strength; and arm F received isavuconazole (Cresemba) as antifungal prophylaxis.

The primary end point for the AUGMENT-101 trial was efficacy as measured by the CR and CRh rate. Secondary end points included duration of response, overall survival, and median relapse-free survival.

Patients with relapsed or refractory acute myeloid leukemia harboring a NPM1 mutation or acute leukemia harboring a KMT2A rearrangement were eligible to enroll on the study. Additional inclusion criteria for both phases of the trial included having an ECOG performance status of 0 to 2, any prior treatment-related toxicities resolved prior to enrollment, and radiation therapy at least 60 days from prior total body irradiation.

Patients were unable to enroll on the trial if they had an active diagnosis of acute promyelocytic leukemia or an isolated extramedullary relapse. Patients were also unsuitable for enrollment if they had an active central nervous system disease, Hepatitis B or C, cardiac disease within 6 months prior to study entry, or gastrointestinal disease.


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 December 6, 2022. yhoo.it/3XYK8jA

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