Syndax Ends Pivotal Leukemia Trial Early as Drug Meets Primary Endpoint

Chronic myeloid leukemia, red blood cell blood smear/iStock

Chronic myeloid leukemia, red blood cell blood smear/iStock

Syndax Pharmaceuticals on Monday announced positive topline data from a pooled analysis of the AUGMENT-101 trial of its menin inhibitor revumenib in adult and pediatric patients with relapsed/refractory KMT2A-rearranged acute myeloid leukemia and acute lymphoid leukemia.

In the Phase I/II AUGMENT-101 study, revumenib demonstrated clinically significant results and met its primary endpoint at the protocol-defined interim analysis stage. Among the 57 patients in the pooled KMT2Ar acute leukemia cohort, there was a complete remission (CR) or a CR with partial hematological recovery (CRh) rate of 23%. In addition, the overall response rate was 63% in efficacy-evaluable patients and the median duration of complete remissions was 9.1 months.

However, despite the announcement of positive trial results, Syndax’s share price was down 9% on Monday. Fierce Biotech reported that the 23% CR/CRh rate in mNPM1 “may be uncompetitive against Kura Oncology, which linked its rival drug candidate ziftomenib to a 30% complete response rate in AML patients with the mutation.”

Still, Syndax decided to stop the pivotal trial to aid with accrual in the KMT2Ar cohorts, citing a recommendation from an Independent Data Monitoring Committee. The company expects to submit a New Drug Application for revumenib as a treatment for R/R KMT2Ar acute leukemia to the FDA by the end of 2023.

According to Ibrahim Aldoss, principal investigator of the AUGMENT-101 trial, there is a critical need for new therapies to treat R/R KMT2Ar acute leukemias as “there are no approved treatments for this population, where currently the expected response rate to standard of care treatment is less than 10%, and the expectation for survival is less than three months.”  

Syndax CEO Michael Metzger said in a statement that the results in the AUGMENT-101 trial “demonstrate the utility of its practice-changing clinical profile and highlight revumenib's potential as a first- and best-in-class agent.”

The drug was well tolerated and consistent with previous data, according to Monday’s announcement. Adverse events leading to dose reductions were minimal. In addition, even though 15% of patients had grade 3 and 1% had grade 4 differential syndrome (DS) compared to zero in the Phase I leukemia cohorts, no patients discontinued the treatment as a result of DS.

Syndax on Monday said that enrollment in the mNPM1 cohort of AUGMENT-101 is progressing smoothly. The company is “funded into the second half of 2025, including through multiple key milestones and both product launches in 2024,” Metzger added.

Matt Olszewski is a freelance writer based in Boston. Reach him on LinkedIn.

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