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iOnctura, a clinical-stage biopharmaceutical company combating neglected and hard-to-treat cancers, announces it has dosed the first patient in its phase I/II clinical trial evaluating roginolisib in patients with myelofibrosis (MF) who are no longer responding to JAK inhibition. Further details of the trial will be presented in a poster presentation at the 67th American Society of Haematology (ASH) Annual Meeting in Orlando, Florida on Sunday, December 7 at 6pm EST.
This milestone marks an important step toward addressing the significant unmet medical needs of MF patients who face diminishing therapeutic options, as their disease progresses or becomes resistant to standard-of-care JAK inhibitor treatment.
The phase I/II trial is part of a comprehensive development program evaluating next-generation PI3Kd inhibitor roginolisib's tolerability and anti-tumour response across a number of solid and hematologic malignancies.
“Based on non-clinical data being presented at ASH, we anticipate that targeting both the PI3Kd and JAK pathways could have a synergistic effect in MF — an approach that has previously eluded older generation PI3Kd inhibitors because of their unfavourable tolerability profiles.” said Dr Michael Lahn, chief medical officer of iOnctura.
Overactivation of the PI3K-Akt signalling pathway contributes to the occurrence and progression of cancer. In MF, pathway activation is a well described mechanism of resistance in response to JAK inhibition . Inhibition of this pathway using roginolisib may overcome the lack of response and lead to a beneficial therapeutic effect. Non-clinical evidence in support of this mechanism is being presented at ASH on Monday, December 8, 2025 at 6 pm EST.
These data demonstrate monotherapy activity of roginolisib against MF cell lines and in vitro models of primary MF cells. Further, roginolisib and JAK inhibition (ruxolitinib or momelotinib) exerts a synergistic anticancer effect. These data support the rationale behind the ongoing HEMA-MED clinical trial.
Professor Alessandro Vannucchi, Professor of Hematology and Department Head of the Center for Research and Innovation in Myeloproliferative Neoplasms (CRIMM) at the University of Florence, Florence, Italy and Principal Investigator of the HEMA-MED study said: “Myelofibrosis patients often have suboptimal responses to ruxolitinib and/or acquire resistance over time. Roginolisib’s intriguing mechanism of action and favourable toxicity profile position it as a compelling partner for ruxolitinib. By combining these agents, we could unlock more durable responses and redefine therapeutic expectations for this challenging rare disease.”
In addition to the two posters related to MF, trials in progress posters for the ongoing investigations of roginolisib in peripheral T-cell lymphoma and chronic lymphocytic leukaemia (CLL) will also be presented at ASH.
MF is a rare myeloproliferative neoplasm marked by activation and growth of mutated cells in the bone marrow, with approximately 0.5 cases per 100,000 individuals diagnosed globally a year.
JAK inhibitors are a key treatment option for MF patients and improve symptoms and quality of life, but approximately half of patients discontinue therapy within three years. Reasons for discontinuation include disease progression, tolerability and adverse events and death resulting from resistance to the JAK therapy.
The HEMA-MED trial (NCT06887803) is a prospective, multi-center, open-label phase I/II single arm trial consisting of two parts. Part 1 (phase 1) will enroll 13 patients to assess the safety of the combination of the PI3Kd inhibitor roginolisib in combination with the JAK inhibitor ruxolitinib, and Part 2 (Phase 2) will expand to enroll 13 additional patients to further allow the assessment of benefit/risk for all 26 patients. In addition to safety, the secondary endpoints of the HEMA-MED trial include blood biomarker and spleen reduction responses, and improvements of MF related symptoms. Exploratory measures will assess endpoints associated with the mechanism of action (MOA) of roginolisib.
Roginolisib is a first-in-class, non-ATP competitive, allosteric modulator of PI3Kd with a unique chemical structure and binding mode. Allosteric modulation is a new archetype for precise inhibition of PI3Kd, promising clinical activity without the detrimental tolerability seen with previous generations of inhibitors.
The PI3K signalling pathway is one of the most commonly dysregulated pathways across multiple cancer.
iOnctura is a clinical-stage precision oncology company combating neglected and hard-to-treat cancers with a pipeline of first-in-class small molecules. The bold new treatments extend lives and improve healthspans, changing the outlook for patients and their families.
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