Syndax Pharmaceuticals, a clinical stage biopharmaceutical company developing an innovative pipeline of cancer therapies, today announced updated positive data from the Phase 1 dose escalation portion of the ongoing Phase 1/2 AUGMENT-101 trial of SNDX-5613 in patients with mixed lineage leukaemia rearranged (MLLr) and nucleophosmin (NPM1c) mutant relapsed/refractory (R/R) acute leukaemias.
SNDX-5613 is the company's highly selective, oral menin inhibitor. Information on how to access the live video webcast and accompanying slide presentation can be found below.
"Data reported today further support the potential for SNDX-5613 to induce clinically meaningful responses in patients with genetically-defined acute leukaemias," said Dr Briggs W Morrison, CEO of Syndax. "Notably, robust clinical activity, including multiple complete responses with no evidence of minimal residual disease (MRD-), were observed in heavily pre-treated MLLr and NPM1c patients. We have identified a candidate recommended Phase 2 dose (RP2D) and expect to commence the pivotal Phase 2 portion of the trial by the end of the second quarter."
"Genetically-defined acute leukaemias, including those harbouring MLLr and NPM1c mutations, represent a disease area with a particularly poor prognosis and few effective treatment options," said Dr Eytan M Stein, assistant attending physician and director, Programme for Drug Development in Leukaemia, department of medicine at Memorial Sloan Kettering Cancer Centre, and the trial's principal investigator. "With five-year survival rates in MLLr and NPM1c mutant acute leukaemias of 50% or less, novel treatments that can offer clinically-meaningful benefit are desperately needed. I am excited to present evidence that underscores previous observations that SNDX-5613 has the potential to disrupt the treatment paradigm for this disease."
As of a 12 March, 2021 data cut-off date, 43 patients with a median of three prior therapies, such as prior stem cell transplant, venetoclax and chemotherapy, were dosed in the Phase 1 portion of the AUGMENT-101 trial. A total of 31 patients were evaluable for efficacy at the time of the data cut-off date, with the remaining patients either not yet at their initial efficacy assessment (n=4) or not harbouring either the MLLr or NPM1c mutation (n=8). The overall response rate1 (ORR) among evaluable patients was 48% (n=15), with 67% (n=10) of these responders achieving MRD negative status, with four of these patients proceeding to receive stem cell transplant. The ORR in evaluable patients harbouring an MLL-rearrangement (n=24), was 54% (n=13), and in evaluable patients harbouring an NPM1c mutation (n=7), was 29% (n=2).
A candidate RP2D of 226 mg every 12 hours was identified for patients who are not receiving a concomitant strong CYP3A4 inhibitor, and 113 mg every 12 hours for patients on a concomitant strong CYP3A4 inhibitor treatment. Eighteen patients treated at the RP2D were efficacy-evaluable and response results observed at the RP2D were consistent with the overall population.
Across all patients enrolled in the trial as of the data cut-off date (n=43), SNDX-5613 was generally well-tolerated, with no discontinuations due to treatment-related adverse events observed in heavily pre-treated patients. The only grade 3 or greater related adverse events occurring in at least 5% of patients were QT prolongation, anaemia, and differentiation syndrome. Among all patients treated at the candidate RP2D (n=22) as of the data cut-off date, 9% of patients (n=2) experienced grade 3 QT prolongation.