Revumenib Demonstrates Activity in Pediatric Patients With KMT2A+ Acute Leukemia


Phase 2 data from the AUGMENT-101 study show that revumenib elicits responses with acceptable safety in pediatric patients with KMT2A+ acute leukemia.

C. Michel Zwaan, MD, PhD

C. Michel Zwaan, MD, PhD

Revumenib (SYNDX-5613) demonstrated similar safety and efficacy in pediatric patients with KMT2A-rearranged acute leukemia to that observed in adult patients, according to data from the phase 2 AUGMENT-101 study (NCT04065399) presented during the 2024 American Society of Pediatric Hematology/Oncology.1

In pediatric patients who comprised the interim analysis efficacy population (n = 13), revumenib induced a complete remission (CR)+CR with partial hematologic recovery (CRh) rate of 23% (95% CI, 5.0%-53.8%) at a data cutoff date of July 24, 2023. In the aggregate population of adults and children (n = 57), the CR+CRh rate was 22.8% (95% CI, 12.7%-35.8%; 1-sided P = .0036), which met the primary end point of the study.

Additional data in the pediatric population revealed that the agent induced a composite CR (CRc) rate of 38.5% (95% CI, 13.9%-68.4%). Moreover, the objective response rate (ORR) achieved with the agent was 46% in this population. Best responses included CR (8%), CRh (15%), CR with incomplete hematologic recovery (8%), CR with incomplete platelet recovery (CRp; 8%), morphological leukemia-free state (MLFS; 8%), disease progression (23%), or other (8%); 3 patients did not respond to treatment.

AUGMENT-101 met its primary efficacy end point in an aggregate population of adults and children with relapsed/refractory KMT2A-rearranged acute leukemia, validating phase 1 results,” C. Michel Zwaan, MD, PhD, a professor of pediatric oncology at Erasmus MC Rotterdam and the Princess Máxima Center in Utrecht, Netherlands, said in a plenary presentation during the meeting. “The majority of responding children, 67%, were able to proceed to transplant, with 2 resuming revumenib maintenance post transplant. The safety profile [of the agent] in children was manageable and consistent with [the] safety profile [observed] in adults.”

Pediatric patients with KMT2A-rearranged acute leukemia experience poor outcomes, and no targeted agents have been approved for this disease. The interaction between menin and KMT2A drives leukemogenesis, but treatment with revumenib disrupts that interaction, according to Zwaan. “By treating the patient with revumenib, the gene transcription signal is off, and this leads to differentiation of leukemia as well as apoptosis of leukemic cells,” he explained.

Data from the phase 1 portion of the trial showed that revumenib elicited responses in patients with relapsed or refractory KMT2A-rearranged and NPM1-mutated acute leukemia, and 67% of those who responded to treatment went on to undergo transplant.2 The agent was also found to have acceptable safety and tolerability. “Moreover, on this trial, children were included, and preliminary antileukemic activity was noted [in them],” Zwaan said. Because revumenib is a substrate of CYP384, two dosages were established – one with and one without a CYP384 inhibitor, he added.

The study enrolled patients with relapsed or refractory acute leukemia who were at least 30 days old and harbored KMT2A rearrangements or NMP1 mutations. Patients received revumenib at the recommended phase 2 dose (RP2D) plus a strong CYP384 inhibitor in 28-day cycles. If their body weight was under 40 kg, the RP2D was 95 mg/m2; if 40 kg or over, they received revumenib at a flat dose of 163 mg. The drug could be given as capsules or an oral solution.

The primary end points of the study were CR+CRh rate and safety. Important secondary end points included CRc and ORR.

A planned interim analysis of patients with KMT2A-rearranged acute leukemia was conducted. The cohort of patients with NPM1-mutated acute myeloid leukemia (AML) is still enrolling, according to Zwaan.

In the efficacy population (n = 13), the median patient age was 5.0 years (range, 1.3-17.0); 23% of patients were under 2 years, 54% were at least 2 years but younger than 12 years, and 23% were at least 12 years but younger than 18 years. Forty-six percent of patients were female and 69% were White. Regarding type of leukemia, 85% had AML and 15% had acute lymphoblastic leukemia. At baseline, 38% of patients had primary refractory disease, 38% had refractory relapsed disease, and 23% had early untreated relapsed disease.

Patients had received a median of 4 prior lines of therapy, with a range of 1 to 11 lines. Notably, 54% of patients had received 3 or more lines of prior treatment. More than half of patients had prior exposure to venetoclax (Venclexta; 62%) and 15% previously received CAR T-cell therapy. Forty-six percent of patients previously underwent hematopoietic stem cell transplant (HSCT), with 15% of those patients having received more than 1 prior transplant.

Additional efficacy data showed that in those who had negative minimal residual disease status by flow cytometry, 2 of 3 patients achieved a CR+CRh and 3 of 5 patients achieved a CRc. Moreover, in all evaluable patients, the median overall survival was 6.9 months (95% CI, 2.3-not reached).

The median time to CR+CRh was 2.27 months (range, 1.0-3.9). Among responders (n = 6), 67% proceeded to HSCT, 50% proceeded to transplant in CR or CRh, and 50% proceeded to transplant in MLFS or CRp. Half of these patients restarted revumenib after HSCT.

In the 23 patients who were evaluable for safety, the adverse effects (AEs) of special interest included grade 2 or higher differentiation syndrome and grade 2 or higher QTc prolongation, and they occurred in 35% and 4% of patients, respectively. Treatment-related AEs that were grade 3 or higher in severity and occurred in at least 10% of patients included febrile neutropenia (13%) and decreased neutrophil count (13%).

One patient experienced an AE that led to discontinuation in the form of febrile neutropenia, and this was not determined to be associated with revumenib.

“The independent NPM1-mutated cohort continues to enroll at all sites,” Zwaan concluded.

In March 2024, the FDA granted priority review to a new drug application (NDA) seeking the approval of revumenib in the treatment of adult and pediatric patients with relapsed/refractory acute leukemia and KMT2A rearrangements.3 The NDA is supported by findings from AUGMENT-101, and has a target action date of September 26, 2024. Previously, in December 2022, the regulatory agency granted revumenib a breakthrough therapy designation for the same indication.4


  1. Zwaan CM, Shukla N, Karras N, et al. Pivotal phase 2 results of AUGMENT-101 for revumenib in KMT2Ar acute leukemia: pediatric experience. Presented at: 2024 American Society of Pediatric Hematology/Oncology; April 3-6, 2024; Seattle, Washington. Abstract 2002.
  2. Issa GC, Aldoss I, DiPersio J, et al. The menin inhibitor revumenib in KMT2A-rearranged or NPM1-mutant leukaemia. Nature. 2023;615(7954):920-924. doi:10.1038/s41586-023-05812-3
  3. Syndax announces FDA priority review of NDA for revumenib for the treatment of relapsed/refractory KMT2Ar acute leukemia. News release. Syndax. March 26, 2024. Accessed April 4, 2024.
  4. 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. December 5, 2022. Accessed April 4, 2024.
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