Revumenib (Revuforj) combined with intensive chemotherapy elicited high levels of response in patients with newly diagnosed acute myeloid leukemia (AML) harboring an NPM1 mutation or KMT2A rearrangement, according to updated data from the phase 1 SNDX-5613-0708 trial (NCT06226571) presented at the
Findings showed that response-evaluable patients across 2 dose levels (n = 35) achieved an objective response rate (ORR) of 97.1% (95% CI, 85.1%-99.9%), comprising a composite complete remission (CRc) rate of 97.1% (95% CI, 85.1%-99.9%) and a CR rate of 77.1% (95% CI, 59.9%-89.6%) as of the November 30, 2025, data cutoff.
The median time to CR was 23.0 days (range, 18.0-70.0). Among patients with evaluable measurable residual disease (MRD) results, 86.2% of those with a CRc (n = 29) and 87.0% of those with a CR (n = 23) achieved MRD negativity by local assessment.
“These updated preliminary efficacy data build upon findings showing deep responses across both dose levels, with high MRD-negative CR rates,” lead study author Ibrahim Aldoss, MD, of City of Hope in Duarte, California, and colleagues wrote in a poster presentation of the data. “Overall, these safety and efficacy findings are consistent in patients with KMT2A-rearranged and NPM1-mutated AML and support continued evaluation of revumenib plus intensive chemotherapy at dose level 2 [DL2] in the phase 3 REVEAL-ND trial [NCT07211958].”
Revumenib is currently approved by the FDA
SNDX-5613-0708 was a multicenter, open-label, nonrandomized, dose-escalation and -expansion study evaluating revumenib plus intensive chemotherapy in patients 18 to 75 years of age with newly diagnosed NPM1-mutated, KMT2A-rearranged, or NUP98-rearranged AML.1 An ECOG performance status of 0 to 2 was required, although those over 65 years of age needed to have a performance status of 0 or 1. Patients also needed to be candidates for intensive chemotherapy. Levels of FLT3-ITD and -TKD mutations needed to be below 3%, and patients could not have plans to receive a FLT3 inhibitor.
At dose level 1 (DL1), patients received revumenib at 110 mg twice per day if they were receiving a strong CYP3A4 inhibitor or 220 mg twice per day without a strong CYP3A4 inhibitor; at DL2, these respective doses were 160 mg twice per day and 270 mg twice per day.
At both dose levels, induction therapy comprised 2 28-day cycles where patients received reumenib on days 8 to 28 plus chemotherapy. Consolidation comprised 4 cycles where revumenib was dosed on days 6 to 26, and patients also received HiDAC; patients who experienced remission were allowed to undergo hematopoietic stem cell transplant (HSCT) at any point from the end of induction but before completing consolidation. After consolidation, revumenib was continued as daily maintenance until disease progression or unacceptable toxicity.
Safety and the incidence of dose-limiting toxicities served as the primary end points. Secondary end points included pharmacokinetic parameters, and efficacy end points were exploratory.
In the overall population across both dose levels (n = 35), the median age was 50.0 years (range, 19.0-73.0). Most patients were female (74%), White (77%), not Hispanic (86%), and had an ECOG performance status of 0 or 1 (92%). Forty percent of patients harbored NPM1 mutations, and 60% had KMT2A rearrangements; no patients harbored NUP98 rearrangements.
Responses were high and similar across both dose levels. In the DL1 cohort, the ORR and CRc rate were both 100% (95% CI, 78.2%-100.0%), and the CR rate was 80.0% (95% CI, 51.9%-95.7%). In the DL2 cohort, the ORR and CRc rate were both 95.0% (95% CI, 75.1%-99.9%), with a CR rate of 75.0% (95% CI, 50.9%-91.3%). MRD-negative CRc was achieved by 83.3% of patients in DL1 (n = 12) and 88.2% in DL2 (n = 17). All 9 evaluable patients treated at DL1 with a CR achieved MRD negativity.
As of the data cutoff, 60% of patients in DL1 (n = 15) and 10% in DL2 (n = 20) had proceeded to HSCT; all patients who underwent transplant had KMT2A-rearranged AML. The investigators attributed the between-cohort difference to the higher proportion of KMT2A rearrangements in DL1 and shorter follow-up in DL2. Among DL1 patients who underwent HSCT (n = 9), 66.7% resumed revumenib maintenance monotherapy at the last tolerated dose.
Any-grade adverse effects (AEs) were reported in 97% of patients (n = 35), and grade 3 or higher AEs occurred in 91%. The most common any-grade AEs were thrombocytopenia/decreased platelet count (60%), febrile neutropenia (60%), diarrhea (54%), and neutropenia/decreased neutrophil count (49%). Revumenib-related AEs occurred in 66% of patients, including grade 3 or higher revumenib-related AEs in 49%, and AEs led to treatment discontinuation in 11% of patients.
One dose-limiting toxicity of grade 3 QTcF prolongation was reported in the DL1 cohort; this patient discontinued revumenib during cycle 1 but achieved an MRD-negative CR and proceeded to HSCT.
Differentiation syndrome, an AE of special interest with menin inhibitors, occurred at grade 3 in 1 patient (5%) treated at DL2, with onset on day 5 and a duration of 2 days that was managed with steroids per protocol guidance. No cases of Hy’s law were reported. One AE leading to death—an intracranial hemorrhage in the DL2 cohort—was deemed unrelated to revumenib.
