ORYZON Shares Early FRIDA Trial Results on Iadademstat and Gilteritinib in FLT3-mut AML at EHA-2024

Data from the initial two cohorts of the FRIDA study have shown promising results regarding the combination of iadademstat and gilteritinib in treating relapsed/refractory acute myeloid leukemia (AML) patients with FMS-like tyrosine kinase mutation (FLT3 mut+). The preliminary findings, presented at the European Hematology Association (EHA) 2024 congress in Madrid, indicate that this drug combination is both safe and effective in this patient population.

The FRIDA study, led by Dr. Amir Fathi from Massachusetts General Hospital, has demonstrated that the iadademstat and gilteritinib combination appears safe and well-tolerated, with no dose-limiting toxicities (DLTs) reported during the 28-day evaluation period for the first two cohorts. These cohorts included six patients in the initial group receiving 100 μg of iadademstat and seven patients in the DL-1 cohort receiving 75 μg of iadademstat. Throughout these cohorts, no unexpected Treatment Emergent Adverse Events (TEAEs) were noted.

The study also reported encouraging antileukemic activity. Bone marrow blast clearance was achieved in 69% of the 13 patients during the first cycle. Moreover, five of these patients experienced complete remission (CR), complete remission with partial hematological recovery (CRh), or complete remission with incomplete blood count recovery (CRi). It is important to note that 11 of the 13 patients were refractory to previous standard regimens such as venetoclax, 7+3 chemotherapy, and midostaurin. Additionally, two patients underwent hematopoietic stem cell transplantation.

Despite the promising results, platelet count recovery has been slow in most patients, which has hindered a rapid transition from a morphologic leukemia-free state (MLFS) to CR/CRh. Given that LSD1 plays a significant role in hematopoiesis and both iadademstat doses showed full LSD1 target engagement, the study has shifted to investigating lower doses to maintain efficacy while improving platelet recovery. This approach aligns with the FDA’s Project Optimus, which aims to identify the minimum safe and biologically active dose.

Currently, the study is enrolling patients for the third cohort (DL-2) with a treatment regimen of 75 μg of iadademstat for three weeks per cycle. Thus far, two patients have been enrolled in this cohort without any reported DLTs. Pharmacokinetic (PK) data from the study support that there is no drug-drug interaction between iadademstat and gilteritinib.

The FRIDA trial is an escalation/expansion, open-label, single-arm, multicenter Phase Ib study designed to establish the safety, tolerability, and recommended Phase II dose (RP2D) of the iadademstat and gilteritinib combination. The study is following the guidelines set by the FDA’s Project Optimus and consists of two parts: a dose-finding segment to evaluate various aspects of the treatment and an expansion segment to further assess its efficacy in patients with FLT3-mutated relapsed/refractory AML. The trial is being conducted in the United States and plans to recruit up to 45 patients.

Oryzon Genomics, the company behind this study, is also expanding the clinical development of iadademstat in AML through an investigator-initiated study (IIS) led by Oregon Health & Science University (OHSU). This upcoming Phase Ib study will evaluate iadademstat in combination with the standard of care (SoC), venetoclax, and azacitidine, in first-line AML patients.

In addition to hematologic cancers, iadademstat is being explored as a potential treatment for solid tumors such as small cell lung cancer (SCLC) and neuroendocrine tumors (NET). A randomized Phase I/II trial for extensive disease small cell lung cancer, combining iadademstat with immune checkpoint inhibitors, is also in the pipeline following recent FDA approval.

Overall, the initial results from the FRIDA study are promising, indicating that the combination of iadademstat and gilteritinib could be a viable treatment option for patients with relapsed/refractory AML with FLT3 mutations. Further studies and expanded cohorts will help determine the optimal dosing and full potential of this therapeutic combination.