FDA Grants Fast Track Designation to SNDX-5613 for the Treatment of Relapsed/Refractory Acute Leukemias

SNDX-5613 has received a fast track designation from the FDA for the treatment of relapsed/refractory acute leukemias, including acute myeloid leukemia and acute lymphoblastic leukemia.

The FDA has granted a fast track designation to SNDX-5613 for the treatment of adult and pediatric acute leukemias that harbor mixed-lineage leukemia rearrangements (MLLr) or NPM1 mutations, according to a press release from drug developer Syndax Pharmaceuticals.1

SNDX-5613—a highly selective, oral, small molecule inhibitor of menin-MLL binding interaction—is currently being evaluated in the open-label, phase 1/2 AUGMENT-101 trial (NCT04065399) in patients with relapsed/refractory acute lymphomas.

“Genetically-defined acute leukemias represent an underserved area marked by particularly poor prognosis and limited therapeutic options,” Briggs W. Morrison, MD, chief executive officer of Syndax, said in a press release. “As we move toward initiating our pivotal study, receipt of fast track designation from the FDA underscores SNDX-5613’s potential to meaningfully improve outcomes for patients with MLLr- and NPM1-mutant acute leukemias.”

In total, 43 patients who had undergone a median of 3 prior lines of therapy had been dosed in the phase 1 portion of the study as of March 12, 2021.2 Thirty-one patients were evaluable for efficacy at the time of data cut off, 4 were not yet at their initial efficacy assessment, and 8 did not harbor either the MLLr or NPM1c mutation.

Findings from an interim analysis of the phase 1 portion of the study indicated that the evaluable population had overall response rate (ORR) of 48% (n = 15), with 67% (n =10) achieving minimal residual disease negativity. Moreover, 4 patients went on to receive stem cell transplantation. Patients harboring an MLLr (n = 24) had an ORR of 54% (n = 13), and those with an NPM1c mutation had an ORR of 29% (n = 2).

The study, which has a target enrollment of 186 participants, featured several cohorts in its phase 1 portion that received escalating doses of the drug with the intent of identifying a maximum tolerated dose and recommended phase 2 dose.The first cohort did not receive any strong cytochrome P450 3A4 inhibitors/inducers, the second was given strong cytochrome P450 inhibitors for antifungal prophylaxis, and the third cohort was treated with a combination of SNDX-5613 and cobicistat (Tybost).

The phase 2 portion of the study will, after determining the recommended phase 2 dose, enroll expansion cohorts, including patients with MLLr acute lymphoblastic leukemia and mixed phenotype acute leukemia, patients with MLLr acute myeloid leukemia (AML), and those with NPM1c AML.

There are several primary outcome measures for the study, some of which include occurrence of dose-limiting toxicities, as well as frequency, duration, and severity of treatment-emergent adverse effects (AEs) in the phase 1 portion and complete remission rate (CR) and frequency and severity of AEs and serious AEs in the phase 2 portion. Secondary outcome measures for the phase 2 portion include composite definition of CR, median relapse-free survival, time to response, duration of response, and overall survival.

SNDX-5613 was previously granted an orphan drug designation for the treatment of those with AML.


  1. SNDX-5613 granted FDA fast track designation for the treatment of relapsed/refractory acute leukemias. News release. Cision. June 28, 2021. Accessed June 29, 2021. https://prn.to/3y5o3lz
  2. Syndax announces positive interim data demonstrating robust clinical activity in phase 1 portion of the AUGMENT-101 trial of SNDX-5613 in patients with genetically-defined acute leukemias. News release. April 20, 2021. Accessed June 29, 2021. https://bit.ly/3x6rKYe
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