Syndax Posts Positive Phase I Data in Genetically-Defined Acute Leukemias

Syndax Pharmaceuticals announced its treatment for mixed-lineage leukemia demonstrated robust clinical activity in a Phase I/II study. Data showed a 48% overall response rate in patients with MLL-r and NPM1 mutant relapsed/refractory (R/R) acute leukemias.

The Phase I study, dubbed AUGMEN-101, assessed SNDX-5613, its investigational, highly selective, oral menin inhibitor. SNDX-5613 is part of an emerging class of drugs that are expected to show potential in treating certain types of genetically-defined leukemias that do not respond well to currently available therapies. 

In its announcement this morning, Syndax said that as of the March 12 cutoff data, 43 patients with a median of three prior therapies, such as the previous stem cell transplant, venetoclax, and chemotherapy, were dosed in the Phase I portion of the AUGMENT-101 trial. At the cutoff date, the company said 31 patients were available for an efficacy assessment. The ORR in evaluable patients harboring an MLL-rearrangement was 54%, and, in evaluable patients carrying an NPM1c mutation, the ORR was 29%.

In addition to the overall response rate, the company said 67% of responders who received the medication during the Phase I portion achieved minimal residual disease-negative status. Based on the data from the Phase I portion, the company has identified the dose levels it intends to use in the Phase II portion of the study, which is expected to begin in the second half of 2021. 

The pivotal Phase II portion of the trial will evaluate the efficacy of SNDX-5613, as defined by complete response rate across three expansion cohorts: MLLr acute lymphoblastic leukemia, MLLr acute myeloid leukemia and NPM1c mutant AML.

Across all patients enrolled in the Phase I portion of the trial who were available for assessment, SNDX-5613 was generally well-tolerated, with no discontinuations due to treatment-related adverse events observed in heavily pretreated patients.

Briggs W. Morrison, chief executive officer of Syndax, said the data from the Phase I portion of the study supports the potential for SNDX-5613 to induce clinically meaningful responses in patients with genetically-defined acute leukemias. 

“Notably, robust clinical activity, including multiple complete responses with no evidence of minimal residual disease (MRD-), were observed in heavily pretreated MLLr and NPM1c patients,” Morrison said in a statement.

"Genetically-defined acute leukemias, including those harboring MLL-r and NPM1 mutations, represent a disease area with a particularly poor prognosis and few effective treatment options," the company said. 

Five-year survival rates in these types of leukemias are below 50%. Eytan M. Stein, director of the Program for Drug Development in Leukemia at Memorial Sloan Kettering Cancer Center and the trial's principal investigator, said novel treatments for these genetically-defined acute leukemias are desperately needed. Evidence from the Phase I portion of the SNDX-5613 study suggests the investigational drug “has the potential to disrupt the treatment paradigm for this disease,” he said. 

SNDX-5613 was granted Orphan Drug Designation by the U.S. Food and Drug Administration to treat patients with AML.