Dapolsertib
Dapolsertib is a selective, small-molecule dual inhibitor of PIM and FLT3 kinases, two enzymes, that play a significant role in the malignant transformation of hematopoietic cells and lymphomagenesis.
Key highlights
The compound has been discovered by Ryvu and is currently in clinical development in collaboration with the Menarini Group as a therapeutic option for various cancers.
Key facts:
- Inhibits lymphoma growth, particularly in ABC-DLBCL.
- Reduces MYC protein levels and MYC-driven gene expression.
- Synergistic with anti-CD20 monoclonal antibodies.
- Well tolerated in in vivo studies and in clinical trials with approx 75 patients with AML.
Originally discovered by Ryvu, dapolsertib was licensed to Menarini and is currently in clinical development, with Ryvu serving as the formal sponsor, as part of a collaboration to explore its potential as a therapeutic option for various cancers.
Figure: Targeted inhibition of PIM kinases in DLBCL by dapolsertib disrupts pro-survival signaling, leading to tumor regression and sensitization to chemotherapy.
Clinical development
Phase I data were generated in AML:
- H1 2017- H1 2021 Phase I dose escalation and cohort expansion in R/R AML – MTD of 125 mg established
- H2 2021 – H1 2023 Phase II expansion cohort in IDH+ R/R AML
- 73 patients dosed across prior studies, including 48 at the R2PD
- Manageable safety profile
- No QTc prolongation, no differentiation syndrome, no gastrointestinal tox
- No hematologic toxicity
JASPIS-01, a Phase II study, is investigating dapolsertib in DLBCL
- Based on strong preclinical evidcence of MEN1703’s activity in lymphoma
- Phase II study consists of two parts: Part 1 pilot cohorts to establish combination dose and monotherapy efficacy followed by Part 2 cohort expansion
- Study locations: USA, Europe
- Phase II study initiated in March 2025
Dapolsertib Pipeline
Clinical program
program
indication
discovery
PRECLINICAL
PHASE I
PHASE II
partner
program
Dapolsertib(PIM/FLT3)
indication
JASPIS-01
DLBCL
(mono and combo with glofitamab)
discovery
PRECLINICAL
PHASE I
PHASE II
partner
For Patients and Caregivers
Dapolsertib is now being evaluated in the JASPIS-01 Phase II trial for relapsed/refractory DLBCL, aiming to assess its safety, efficacy, and therapeutic potential as both a monotherapy and in combination with standard treatments.
Contact
FOR MEDICAL PROFFESIONALS & INVESTIGATORS
If you are a medical professional, an investigator for a RYVU trial, or would like information about becoming an investigator, please contact us at [email protected] or use contact form.
