NEWTOWN, PA — Onconova Therapeutics, Inc. (NASDAQ: ONTX), a clinical-stage biopharmaceutical company focused on discovering and developing novel products for patients with cancer, announced the publication of a preclinical study in the journal Molecular Cancer.
The study, entitled “Novel induction of CD40 expression by tumor cells with RAS/RAF/PI3K pathway inhibition augments response to checkpoint blockade,” showed that rigosertib synergistically enhanced the efficacy of ICB in a murine melanoma model via the induction of immune-mediated cancer cell death.
“The data from this recent publication demonstrate rigosertib’s potential to address a pressing unmet need, as many patients do not respond to immune checkpoint blockade due to immunosuppressive tumor microenvironments,” said Ann Richmond, Ph.D., Ingram Professor of Pharmacology and Medicine at the Vanderbilt University School of Medicine and lead author of the study.
“By reversing immunosuppressive tumor microenvironments, rigosertib overcame pro-tumor resistance mechanisms and synergistically enhanced the efficacy of immune checkpoint blockade in a difficult-to-treat murine melanoma model. These compelling findings provide preclinical proof-of-concept for rigosertib-immune checkpoint blockade combination therapy and strongly support its evaluation in clinical trials.”
Key data and conclusions from the recent publication include:
- Rigosertib treatment enhanced the activation of anti-cancer immune cells and increased the frequency of these cells in the tumor microenvironment (TME).
- Rigosertib treatment reduced the frequency of pro-tumor CD206+ M2-like macrophages in the TME.
- Rigosertib monotherapy rapidly reduced PI3K signaling with induction of CD40 expression, leading to melanoma cell death and inhibition of tumor growth in vivo due to its ability to promote the tumor infiltration of activated anti-cancer immune cells.
- Rigosertib’s ability to remodel the TME enabled it to synergistically combine with ICB and improve tumor growth inhibition and survival in a mouse model of melanoma that did not respond to ICB alone, or a clinically used combination of ICB plus BRAF and MEK inhibitors.
Steven M. Fruchtman, M.D., President and Chief Executive Officer of Onconova, added, “We are very pleased with these recently published results, which will inform the data driven approach guiding our clinical rigosertib investigator-initiated study program. They provide strong mechanistic support for both the ongoing KRAS mutated non-small cell lung cancer trial of rigosertib in combination with a check point inhibitor and a potential trial in patients with advanced melanoma evaluating a rigosertib-checkpoint inhibitor combination that is under active consideration. Looking ahead, we plan to continue leveraging our collaborations with leading institutions such as Vanderbilt University as we pursue opportunities for rigosertib while maintaining our primary focus and resources on our lead ON 123300 multi-kinase inhibitor program.”
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