Syndax reports new data from AUGMENT-102 trial

The company announced a poster presentation featuring updated data from the AUGMENT-102 trial of revumenib in combination with fludarabine/cytarabine in a predominantly pediatric population of patients with relapsed/refractory mNPM1, NUP98-rearranged or KMT2Ar AML titled “Safety and Activity of Revumenib in Combination with Fludarabine/Cytarabine in Patients with Relapsed/Refractory Acute Leukemias.” As of the data cutoff date of January 15, 2024, 27 patients received revumenib plus FLA, including 9 patients treated at 113 mg q12h and 18 treated at 163 mg q12h. The patients enrolled had a median age of 6 years and had received a median of 3 prior lines of therapy. Eighteen patients had prior FLA containing regimens while 11 patients had prior HSCT. Five patients treated at the 113 mg q12h dose and nine patients treated at the 163 mg q12h achieved a CRc. Most patients who achieved a CRc and had evaluable data achieved negative status and 7 patients underwent HSCT while in remission following treatment. Overall, revumenib was tolerable in heavily pretreated patients with KMT2Ar, NUP98r, or NPM1m acute leukemias without increased frequency or severity of AEs compared with historic FLA data or revumenib monotherapy. One DLT occurred at the 163 mg q12h dose that was a Grade 4 decreased neutrophil count in a patient with multiple prior transplants. Grade 3 and above adverse events in over 40% of patients included decreased platelet count, anemia and febrile neutropenia. Lower rates of cytopenias were reported at the 163 mg q12h dose than the 113 mg q12h dose, consistent with faster remission at the higher dose. Lower rates of nonhematologic adverse events were also observed at the higher dose level, which further suggests that the adverse event profile was not driven by revumenib. There was one adverse event leading to death not related to revumenib. There were no cases of differentiation syndrome in the trial. This study supports the selection of revumenib 163 mg q12h combined with FLA and a strong cytochrome P450 inhibitor as the RP2D, in line with the dose of revumenib under FDA review as a monotherapy agent.