NMS-088 / Nerviano Medical Sciences - LARVOL DELTA

MKIA-088-001: Study of NMS-03592088 in Patients With Relapsed or Refractory AML or CMML (clinicaltrials.gov) - P1/2 | N=63 | Terminated | Sponsor: Nerviano Medical Sciences | N=200 ➔ 63 | Trial completion date: Feb 2026 ➔ Aug 2024 | Recruiting ➔ Terminated | Trial primary completion date: Dec 2025 ➔ Aug 2024; Study stopped due to strategic reasons. The decision is not based on specific safety findings as the safety observed in the phase II part of the study is in line with what was reported in the phase I part.

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • FLT3

Nerviano Medical Sciences announces strategic portfolio shaping. (NMS Group) - "Nerviano Medical Sciences S.r.l...announces the strategic discontinuation of three development programs to further prioritize and reinforce efforts on core programs. NMS-088...The decision is the result of internal analysis of the benefit profile of the drug in the third line (3L) setting in patients who are refractory or relapsed after standard of care including prior FLT3 inhibitors and considering the further development in rapidly changing AML treatments. NMS will report the data in in the first half of 2025...NMS-173, a potent covalent orally available, second-generation dual IDH1/ IDH2 inhibitor...NMS-341, a late preclinical-stage next-generation inhibitor of CDC7..."

Clinical data • Discontinued • Acute Myelogenous Leukemia • Biliary Tract Cancer • Cholangiocarcinoma • Hematological Malignancies • Leukemia • Oncology • Solid Tumor

Study of NMS-03592088 in Patients With Relapsed or Refractory AML or CMML (clinicaltrials.gov) - P1/2 | N=200 | Recruiting | Sponsor: Nerviano Medical Sciences | N=140 ➔ 200 | Trial completion date: Sep 2023 ➔ Feb 2026 | Trial primary completion date: Sep 2023 ➔ Dec 2025

Enrollment change • Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • FLT3

NMS-088, which inhibits FLT3, KIT, and CSF1, may be useful for FLT3 mutation-positive relapsed/refractory AML treated with FLT3 inhibitor [AACR 2023] [Google translation] (Nikkei) - P1/2 | N=140 | NCT03922100 | "NMS-088 demonstrated manageable safety and no MTD was identified. Patients receiving 360 mg on schedule A experienced 3 DLTs with grade 3 or greater postural abnormalities, hypoactivity, and dyspnea....Anti-tumor effects were observed only in FLT3 mutation-positive patients. Twenty-one patients with FLT3-mutant AML were evaluable for antitumor efficacy and received doses of 120 mg to 360 mg on Schedule A or B. Patients receiving doses greater than 180 mg responded as assessed by the study group, with 3 CRi and 2 MLFS (morphologic leukemic cell-free state)....Long-term (>7 cycles) stable disease was also achieved in three of the patients who received doses of 180 mg or less."

P1/2 data • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

NMS-03592088, a novel, potent FLT3, KIT and CSF1R inhibitor with activity in FLT3 positive acute myeloid leukemia patients with prior FLT3 inhibitor experience (AACR 2023) - "Despite the approval of midostaurin and gilteritinib, the prognosis for FLT3+ patients with relapsed or refractory disease is poor. NMS-088 showed clinical efficacy in pts with FLT3+ R/R AML, including pts who have failed prior FLT3 inhibitors. Together with the manageable safety observed, these results warrant further development of this drug including potential as a novel valuable therapeutic option for pts who have exhausted available treatments. The trial is currently opened for enrollment (NTC03922100)."

Clinical • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • FLT3

"FLT3、KIT、CSF1を阻害する #NMS088 が、FLT3阻害薬の投与歴がある #FLT3変異 陽性の再発・難治性 #急性骨髄性白血病（#AML）に有用である可能性が明らかとなりました。 #AACR23 https://t.co/OVLDIm1tgO" (@cancer_navi)

Acute Myelogenous Leukemia • Oncology • CSF1

Study of first administration in humans and efficacy of NMS-03592088, an inhibitor of FLT3, KIT and CSF1R, in patients with Relapsing or Drug-resistant Acute Myeloid Leukemia (LMA) and Chronic Myelomonocytic Leukemia (LMMC). Studio di prima somministrazione nell'uomo e di efficacia di NMS-03592088, un inibitore di FLT3, KIT e CSF1R, in pazienti con Leucemia Mieloide Acuta (LMA) e Leucemia... (clinicaltrialsregister.eu) - P1/2; N=165; Ongoing; Sponsor: NERVIANO MEDICAL SCIENCES SRL

Clinical • New P1/2 trial • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • FLT3

Study of NMS-03592088 in Patients With Relapsed or Refractory AML or CMML (clinicaltrials.gov) - P1/2; N=140; Recruiting; Sponsor: Nerviano Medical Sciences

Clinical • New P1/2 trial • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • Oncology • FLT3

A Phase I/II Study of NMS-03592088, a FLT3, KIT and CSF1R Inhibitor, in Patients with Relapsed or Refractory AML or CMML (ASH 2019) - "In a FLT3-ITD model of disseminated AML, efficacy observed following single agent treatment with NMS-03592088 was further significantly increased when administered in combination with cytarabine, with excellent tolerability. Exploratory endpoints are included to evaluate the potential effects of treatment with NMS-03592088 on circulating levels of CSF1 in plasma, the potential correlation of cellular CSF1R expression levels with clinical outcome in both AML and CMML, and the mutational status of a panel of leukemia-related genes, not limited to FLT3. The Phase I part started in Italy in March, 2019 and is currently ongoing."

Clinical • P1/2 data • CSF1R • FLT3