Nerviano Medical Sciences Announces Phase 1 Clinical Trial Data for NMS-03592088 in Patients with FLT3 positive Relapsed or Refractory Acute Myeloid Leukemia
April 16, 2023

Nerviano 16 April 2023_Nerviano Medical Sciences Srl, a member of NMS Group and a clinical stage company discovering and developing innovative therapies for the treatment of cancer, today announced that data from the First-In-Human study of NMS-03592088, a novel, potent inhibitor of FLT3, KIT and CSF1R were presented during an oral scientific session at the American Association for Cancer Research 2023 Annual Meeting in Orlando, Florida.

NMS-03592088 is an orally available compound that showed superior preclinical activity with respect to first and second generation FLT3 inhibitors and demonstrated a good potency on resistance mutation F691L identified as cause of relapse in patients treated with selective FLT3 inhibitors. NMS-03592088 is currently being explored in MKIA-088-001 trial, a multi-center Phase 1/2 study to evaluate safety, tolerability and efficacy in patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) or chronic myelomonocytic leukemia (CMML).

The Phase 1 portion of the study was a 3+3 design dose escalation with NMS-03592088 administered daily for 21 of 28 days (schedule A) or continuously (schedule B). As of January 26, 44 R/R AML or CMML patients were treated across doses from 20 to 360 mg/day in schedule A or from 120 to 250 mg/day in schedule B. 41 patients had AML and 3 patients had CMML. 24 AML patients were FLT3 positive with FLT3-ITD mutations representing the most common genetic alteration and the majority of them had received at least one prior FLT3 inhibitor (87.5%).

NMS-03592088 showed manageable safety with no maximum tolerated dose characterized. Overall, the most frequent treatment-emergent related adverse events were nausea (any grade, 20.5%), vomiting (13.6%), asthenia (11.4%). A dose-dependent trend of reversible myasthenic syndrome was also characterized.

In terms of clinical benefit, the data showed a dose-dependent trend for response. 5 out of 12 evaluable patients with FLT3 positive AML treated at dose ≥ 300 mg achieved an investigator-assessed response. All these patients had received prior midostaurin and 2 had received prior midostaurin and prior gilteritinib. Two patients with response were able to withdraw from study to receive HSCT.  Overall, the duration of response ranged from 1.3-7.9 months.

In summary, NMS-03592088 showed clinical efficacy in patients with FLT3 positive R/R AML, including patients who have failed prior FLT3 inhibitors. These results, together with the manageable safety observed, warrant further development which is now being explored in Phase 2 trial.

“We are pleased to see that NMS-03592088 demonstrates antileukemic activity in FLT3 positive AML patients since these patients are at high risk for poor outcomes” was noted by Lisa Mahnke, MD, PhD, Chief Medical Officer for Nerviano Medical Sciences.   

“We believe that despite availability of FLT3 targeted agents there is still need for more effective treatments, including those for patients that have failed current FLT3 inhibitors“ according to Hugues Dolgos, PharmD, CEO, Nerviano Medical Sciences.  

A copy of today’s presentation “NMS-03592088, a novel, potent FLT3, KIT and CSF1R inhibitor with activity in FLT3 positive acute myeloid leukemia patients with prior FLT3 inhibitor experience“  is available at this link:

About Acute Myeloid Leukemia

Acute Myeloid Leukemia (AML) is a rapidly progressing hematologic malignancy that most frequently develops in older adults. FLT3 mutations occur in approximately 30% of AML patients and are associated with aggressive disease, higher relapse rates and worse survival. Despite the approval of FLT3 inhibitors midostaurin and gilteritinib the prognosis of patients with relapsed or refractory disease is poor.

About NMS-03592088

NMS-03592088 is a novel, potent inhibitor of FLT3, KIT and CSF1R, all relevant targets in AML. NMS-03592088 showed superior preclinical activity compared with approved FLT3 inhibitors in different FLT3-driven models. In addition, NMS-03592088 is active on FLT3 gatekeeper mutation F691L causing resistance to first generation FLT3 inhibitors. NMS-03592088 is being developed in AML with two studies currently recruiting (MKIA-088-001 and MKIA-088-002)

Link: AACR2023_FLT3_ Press release16 April 2023


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