Novel TIE2 Kinase Inhibitor Under Study in Platinum-Resistant Ovarian Cancer
Posted: Sunday, November 1, 2020
In part 1 of a phase Ib/II study conducted by Erika P. Hamilton, MD, of the Sarah Cannon Research Institute-Cancer Centre, Nashville, and colleagues, rebastinib in combination with paclitaxel demonstrated antitumor activity across multiple tumor types. Part 2 of the study includes five cohorts: triple-negative breast cancer, inflammatory breast cancer, platinum-resistant ovarian cancer, endometrial cancer, and carcinosarcoma. Preliminary results from the platinum-resistant ovarian cancer cohort were presented during the European Society for Medical Oncology (ESMO) Virtual Congress 2020 (Abstract 839P).
“Rebastinib is a switch control inhibitor of TIE2 kinase,” the investigators remarked. “TIE2 is expressed in endothelial cells and in some macrophages with proangiogenic, prometastatic, and immunosuppressive properties associated with chemotherapy resistance.”
Part 2 is a Simon 2-stage design; enrollment is ongoing. The study was designed to enroll a total of 18 patients in the first stage and an additional 15 patients in the second stage if at least 5 patients achieved a response. Patients with heavily pretreated advanced or metastatic platinum-resistant ovarian cancer were administered rebastinib in combination with weekly paclitaxel. All patients received at least one prior regimen with paclitaxel or carboplatin. As of March 20, 2020, a total of 20 patients were enrolled.
Of the 17 evaluable patients, 5 achieved a partial response, and 9 had stable disease at 8 weeks. The objective response and clinical benefit rates were 29% and 82%, respectively. A CA-125 response was observed in more than half (62%) of patients.
Most treatment-emergent adverse events were grade 2 or lower; fatigue, nausea, diarrhea, dry mouth, peripheral sensory neuropathy, vomiting, abdominal pain, alopecia, constipation, peripheral edema, and stomatitis were reported. The investigators observed three serious adverse events possibly related to rebastinib: grade 2 reversible muscular weakness, fatigue,; and constipation.
Disclosure: For full disclosures of the study authors, visit oncologypro.esmo.org.