| Title: |
Dual FLT3/PIM inhibitor dapolsertib in acute myeloid leukemia: results from the phase 1/2 DIAMOND-01 trial |
| Authors: |
Martinelli G.; Solomon S. R.; Mukherjee S.; Santoro A.; Strickland S. A.; Vives S.; Ravandi F.; Walter R. B.; Cook R. J.; Lech-Maranda E.; Calbacho M.; Wierzbowska A.; Marconi G.; Acuña-Cruz E.; Cano-Ferri I.; Bertolini F.; Rzymski T.; Paoli A.; Merlo G. M.; Auriol F. K.; Zicari S.; Galleu A.; Gupta I.; Montesinos P. |
| Contributors: |
Martinelli, G.; Solomon, S. R.; Mukherjee, S.; Santoro, A.; Strickland, S. A.; Vives, S.; Ravandi, F.; Walter, R. B.; Cook, R. J.; Lech-Maranda, E.; Calbacho, M.; Wierzbowska, A.; Marconi, G.; Acuña-Cruz, E.; Cano-Ferri, I.; Bertolini, F.; Rzymski, T.; Paoli, A.; Merlo, G. M.; Auriol, F. K.; Zicari, S.; Galleu, A.; Gupta, I.; Montesinos, P. |
| Publication Year: |
2026 |
| Collection: |
IRIS Università degli Studi di Bologna (CRIS - Current Research Information System) |
| Subject Terms: |
leukemia |
| Description: |
Acute myeloid leukemia (AML) is an aggressive hematopoietic cancer with poor survival outcomes. Despite improvements with recent FMS-like tyrosine kinase 3 (FLT3) inhibitors, resistance is common, and responses are short. Dapolsertib (MEN1703) is a novel, first-in-class dual inhibitor of PIM (proviral integration site for Moloney murine leukemia virus) and FLT3 kinases, with activity in both FLT3-mutated and wild-type cells. A phase 1/2 open-label, multicenter, dose-escalation study (DIAMOND-01) investigated the maximum tolerated dose (MTD) of single-agent dapolsertib and assessed its safety, efficacy, pharmacokinetic (PK) profile, pharmacodynamic biomarkers, and genomics in patients with AML with no standard therapeutic options available. Seventy-three patients received oral doses of dapolsertib ranging from 25 to 150 mg per day (14 consecutive days over 21-day cycles). In the dose-escalation phase, the MTD was 125 mg and was selected for dose expansion. The most common grade ≥3 adverse events in patients receiving 125 mg were pneumonia (38%), thrombocytopenia (30%), and anemia (27%); most of these events were deemed not treatment related. For patients receiving 125 mg dapolsertib (n = 55), the overall response rate was 9%, with a median 2.07-month duration of response, and 4 of 5 responses were observed in patients with isocitrate dehydrogenase 1 (IDH1)/IDH2 mutations. PK analysis indicated rapid absorption of oral dapolsertib, an elimination half-life suitable for once daily dosing and a PK independent of formulation and IDH mutational status. Pharmacodynamic activity was confirmed in 50% of evaluable patients. Overall, dapolsertib demonstrated modest single-agent activity in patients with AML. This trial was registered at www.clinicaltrials.gov as #NCT03008187. |
| Document Type: |
article in journal/newspaper |
| File Description: |
ELETTRONICO |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/41536779; volume:3; issue:1; firstpage:1; lastpage:1; numberofpages:1; journal:BLOOD NEOPLASIA; https://hdl.handle.net/11585/1039151 |
| DOI: |
10.1016/j.bneo.2025.100178 |
| Availability: |
https://hdl.handle.net/11585/1039151; https://doi.org/10.1016/j.bneo.2025.100178 |
| Accession Number: |
edsbas.BC6BA744 |
| Database: |
BASE |