Ryvu Therapeutics announced today that the first patient has been dosed in the JASPIS-01 study, a Phase II clinical trial investigating dapolsertib (MEN1703, SEL24) for the treatment of relapsed/refractory (r/r) diffuse large B-cell lymphoma (DLBCL). The trial will evaluate the dual PIM/FLT3 kinase inhibitor both as a monotherapy and in combination with glofitamab.
The JASPIS-01 study was initiated at clinical sites in Poland, with expansion to additional EU and non-EU locations already underway. The study is fully funded by Menarini Group and executed by Ryvu Therapeutics.
Novel Dual Kinase Inhibitor Targets Aggressive Lymphoma
Dapolsertib hydrochloride, recently recognized by the World Health Organization (WHO) as the approved International Nonproprietary Name (INN) for MEN1703 (SEL24), is a selective, small-molecule dual inhibitor of PIM and FLT3 kinases. These enzymes play significant roles in the malignant transformation of hematopoietic cells and lymphomagenesis.
"DLBCL remains a challenging disease with limited treatment options, particularly in the relapsed/refractory setting," said Hendrik Nogai, M.D., Chief Medical Officer of Ryvu Therapeutics. "We believe that dapolsertib, with its novel dual inhibition of PIM and FLT3 kinases, holds the potential to offer meaningful therapeutic benefits to these patients."
The compound was discovered by Ryvu and is being developed in collaboration with the Menarini Group following a licensing agreement signed in March 2017, under which Menarini holds global development and commercial rights.
Comprehensive Three-Part Clinical Trial Design
The JASPIS-01 study is designed as an open-label, Phase II clinical trial with three distinct parts:
- Part 1 will focus on evaluating safety and preliminary anti-tumor activity in approximately 18 patients
- Part 2 will assess anti-tumor activity as a primary objective in a larger patient cohort, along with safety and tolerability
- Part 3 will offer an optional randomized comparison to demonstrate the contribution of dapolsertib and glofitamab over glofitamab alone
The study is registered on ClinicalTrials.gov under identifier NCT06534437.
"We are excited to progress dapolsertib into a Phase II clinical trial in relapsed/refractory DLBCL," said Nassir Habboubi, MD, Chief Medical Officer of Stemline Therapeutics, a wholly-owned subsidiary of the Menarini Group. "By evaluating dapolsertib as a monotherapy and in combination with glofitamab, we hope to demonstrate its potential to address this difficult-to-treat cancer."
Building on Previous Clinical Experience
Dapolsertib was initially developed as a potential treatment for patients with relapsed/refractory acute myeloid leukemia (r/r AML). A Phase I/II clinical study in AML (NCT03008187) has been completed, with data presented at various scientific conferences.
Encouraged by promising results from translational research, Menarini decided to continue development by initiating the new Phase II study in r/r DLBCL. Translational work in other hematologic indications is also ongoing.
Addressing an Unmet Medical Need
DLBCL is the most common type of non-Hodgkin lymphoma, accounting for approximately 30-40% of all cases. Despite advances in treatment, a significant portion of patients experience relapse or become refractory to initial therapy, creating a substantial unmet medical need.
The primary goal of the JASPIS-01 study is to assess both the safety and anti-tumor activity of dapolsertib in this difficult-to-treat patient population. The inclusion of both monotherapy and combination therapy arms with glofitamab provides multiple potential pathways to clinical benefit.
"This study is a major step forward in our partnership with the Menarini Group, and we look forward to advancing this program," added Dr. Nogai.
About Ryvu Therapeutics
Ryvu Therapeutics is a clinical-stage drug discovery and development company focused on novel oncology therapies that address emerging targets. The company's internally discovered pipeline includes small molecules and antibody-drug conjugates directed at kinases, synthetic lethality, and immuno-oncology targets.
In addition to dapolsertib, Ryvu's most advanced program is RVU120, a selective CDK8/CDK19 kinase inhibitor currently in Phase II development for hematological malignancies. The company is also advancing RVU305, a potentially best-in-class, brain-permeable PRMT5 inhibitor for multiple solid tumors, currently in IND/CTA-enabling studies.
Founded in 2007 and headquartered in Kraków, Poland, Ryvu Therapeutics is listed on the Warsaw Stock Exchange and is a component of the sWIG80 index.
