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- Onconova - Rigosertib - Small Molecule
Onconova - Rigosertib - Small Molecule
Rigosertib is a small molecule that inhibits multiple cellular signaling pathways driving cancer cell growth while having little effect on normal cells. In contrast to many kinase inhibitors, rigosertib does not interact at the ATP binding site, but acts via allosteric inhibition. Rigosertib has the potential to affect three critical pathways for cancer cell proliferation and survival: the RAS/RAF/MEK/ERK, the PI3K/AKT and the PLK1 pathways. In addition, rigosertib may be a potent immunomodulator via the stimulation of neoantigen expression resulting in attraction of immune cells into the tumor microenvironment and thus making the tumor more susceptible to immunotherapy.
Rigosertib has been shown to mediate disruption of RAS/RAF dimerization (Athuluri-Divakar 2016, Liu 2020) repression of PI3K/AKT activity (Chapman 2012, Xu 2014, Hyoda 2015, Prasad 2016), induction of reactive oxygen species (ROS) pathway through activation of the Jun Kinase (JNK) enzyme (Chapman 2012, Ritt 2016, Gunther 2020), and inhibition PLK-1 activity (Gumireddy 2005, Athuluri-Divakar 2016, Atanasova 2020). Interference of multiple growth and survival pathways, especially activated RAS, resulting in cell cycle arrest and apoptosis, provides a unique opportunity to target multiple cancer types without generating resistant clones.
Rigosertib Plus Nivolumab for KRAS+ NSCLC Patients Who Progressed on First-Line Treatment
Phase 1/2a (NCT04263090)
This is an open-label, Phase 1/2a study incorporating a dose-escalating stage followed by a dose-expansion stage to study the combination of rigosertib and nivolumab in metastatic Kirsten rat sarcoma positive (KRAS+) lung adenocarcinoma patients who have progressed on standard first line treatment.
Status: Recruiting
Rigosertib in Recessive Dystrophic Epidermolysis Bullosa-Associated Squamous Cell Carcinoma
Phase 2 in Austria and England
This is a Phase 2 open study to assess efficacy and safety of rigosertib in patients with recessive dystrophic epidermolysis bullosa (RDEB)-associated locally advanced/metastatic squamous cell carcinoma (SCC).
Status: Recruiting