The company is developing a pipeline of cancer therapies and made the announcement yesterday (October 3) about data from the protocol-defined pooled analysis from the trial of ruvumenib, a small molecule inhibitor.
The trial called Augment-101 included adult and pediatric patients with relapsed/refractory (R/R) KMT2A-rearranged (KMT2Ar) acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL).
The trial met its primary endpoint at the protocol-defined interim analysis stage with a complete remission or with partial hematological recovery rate of 23% among the 57 efficacy evaluable patients in the pooled KMT2Ar acute leukemia cohort.
Practice-changing clinical profile
“We are thrilled to report positive results for revumenib in KMT2Ar acute leukemia that demonstrate the utility of its practice-changing clinical profile and highlight revumenib's potential as a first- and best-in-class agent,” said Michael Metzger, chief executive officer of Syndax.
“Breakthrough Therapy Designation has enabled us to work closely with the FDA to submit an NDA by year-end. Enrollment in the mNPM1 cohort of Augment-101 is also progressing well, and we are rapidly advancing that program to an anticipated filing following KMT2Ar. Syndax is funded into the second half of 2025, including through multiple key milestones and both product launches in 2024, which will put us on a clear path to realize the full blockbuster potential of revumenib and axatilimab.”
The remission rates in patients with KMT2Ar AML was 24.5%. The complete or partial remission responses in both the overall population and the AML subset were durable with a 6.4-month median duration as of the July 24, 2023 data cut-off, with 46% remaining in response. Minimal residual disease (MRD) status was assessed in 10 of the 13 patients who achieved a complete or partial remission, 70% of whom were MRD negative.
Hematopoietic stem cell transplant
A total of 39% of patients who achieved an overall response underwent hematopoietic stem cell transplant (HSCT), eight of whom did not achieve a complete or partial remission response prior to transplant. Half of the patients who had an HSCT received post-transplant maintenance with revumenib and three additional patients (21%) were in follow-up and are eligible to restart revumenib as post-transplant maintenance.
Based on the Independent Data Monitoring Committee (IDMC) recommendation, the company is stopping the trial to further accrual in the KMT2Ar cohorts. Syndax continues to expect to submit an NDA for revumenib for the treatment of R/R KMT2Ar acute leukemia to the US Food and Drug Administration (FDA) by the end of the year.
Ibrahim Aldoss is assistant attending physician and associate professor, division of leukemia, department of hematology and hematopoietic cell transplantation at the City of Hope, and principal investigator in the AUGMENT-101 trial.
Critical need for new therapies
“There is a critical need for new therapies to treat R/R KMT2Ar acute leukemias. 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. This pivotal dataset of revumenib monotherapy in heavily pretreated R/R patients is very compelling in that it demonstrates significant clinical benefit that includes deep molecular remissions and is well tolerated
"The responses were durable with a high proportion of patients proceeding to potentially curative transplant and re-starting revumenib therapy. This is especially impressive given that these patients would generally not have an option for transplant with the current treatment options."