Orally administered rigosertib was found to be well-tolerated in patients with advanced solid tumors in a phase 1 trial. Rigosertib is a dual kinase inhibitor, and this trial is the first to study its orally administered form in solid tumors. Intravenously administered rigosertib is already in phase 3 clinical trials for myelodysplastic syndrome (MDS) and pancreatic cancer. Oral rigosertib is being studied in a pair of phase 2 trials in lower-risk transfusion-dependent MDS patients.
Overall, 48 patients were included in the phase 1 trial with oral rigosertib, and seven remained on study for at least 6 months. Six head and neck cancer patients included in this study had failed platinum-based therapies, and two of these patients showed a response to rigosertib—one with the disappearance of lung metastasis and another with greater than 50% decrease of liver metastasis. These two patients have received oral rigosertib treatment for 98 and 48 weeks.
“The results from the head and neck cancer patients are interesting, revealing that the drug worked in a subset of patients,” said Antonio Jimeno, MD, PhD, investigator at the University of Colorado Cancer Center in Denver and director of the university’s Head and Neck Cancer Medical Oncology Program. “To learn more about the relationship between response and genetic make-up of the tumor, we’ve been investigating molecular correlates in a surrogate phase 2 trial in patient-derived animal models of head and neck cancer.”
As highlighted in the presentation at the American Association for Cancer Research annual conference in Washington, DC, several potential biomarkers were detected through genetic analysis of tumor samples from the phase 1 trial and continuing genetic analysis of animal models. The potential biomarkers include the genes PIK3CA and PTEN, which are both members of the signaling pathway targeted by the drug. Whole-exome sequencing of patient samples also revealed what Jimeno called, “a short list of core alterations in genes for further exploration as predictive biomarkers.”
“These promising results from human trial combined with relevant animal models established in our laboratories are helping us learn more about this drug and its mechanism of action. Based on these studies, we are initiating an 80-patient, multi-institutional phase 2 trial,” said Jimeno. In this trial, tissue samples from patients will be analyzed by sequencing and using other genomic tools to fully explore the predictive capability of these candidate biomarkers.
“We have seen meaningful activity in a subset of patients in the Phase 1 trial and we confirmed this in the surrogate animal model,” Jimeno said. “The hope is that broad genetic analysis will help identify biomarkers for accurately matching the drug with the right patients in the future.”
“It’s an exciting time for an exciting drug,” Jimeno said.