FDA fast tracks zotiraciclib for treating aggressive brain cancer
New designation aims to speed development of oral glioma therapy
The U.S. Food and Drug Administration (FDA) has granted fast track status to zotiraciclib (ZTR/TG02) — an oral medication that targets pathways in the body that are used by tumor cells — as a potential treatment for certain aggressive forms of glioma.
The designation, which aims to expedite the development of therapies with the potential to address unmet needs in the management of serious health conditions, specifically covers the use of zotiraciclib as a treatment for recurrent high-grade gliomas harboring IDH1 or IDH2 mutations. High-grade glioma is characterized by rapid, aggressive growth that spreads quickly into surrounding brain tissue.
The new designation provides zotiraciclib’s developer Cothera Bioscience with perks that include more frequent communication with the FDA during the drug development process.
“Receiving FDA fast track designation for zotiraciclib marks a pivotal moment in our mission to improve outcomes for patients with [recurrent high-grade gliomas harboring IDH1 or IDH2 mutations],” Vernon Jiang, PhD, Cothera’s executive vice president of research and development, said in a company press release announcing the new status.
An oral therapy, zotiraciclib is designed to inhibit several cellular pathways that tumor cells use to grow and avoid death.
The FDA’s decision to grant the investigational therapy fast-track status was supported by the completion of the Phase 1 portion of an ongoing Phase 1/2 clinical trial (NCT05588141). The study, which is open to patients ages 15 and older, is recruiting participants at a site in Maryland. The trial is sponsored by the U.S. National Cancer Institute (NCI), part of the National Institutes of Health.
The Phase 1 study findings were shared last month at the annual meeting of the World Federation of Neuro-Oncology Societies and the Society for Neurooncology, held in Honolulu. The presentation was titled “Phase I/II study of zotiraciclib for recurrent malignant gliomas with IDH mutations: Results of the Phase I study.”
Early trial results helped set zotiraciclib dose at 200 mg
In that first phase, researchers evaluated safety outcomes in 12 patients who were treated with zotiraciclib as monotherapy, or alone, without other medications. The main goal was to look for dose-limiting toxicities — safety issues that suggest the dose of the therapy is too toxic to be ethically used as a medicine — and determine the recommended Phase 2 dose.
All participants received the oral therapy twice a week for the first three weeks of every 28-day treatment cycle. Six patients received a dose of 200 mg/day; no dose-limiting toxicities were reported in these patients. The other six patients took a higher dose of 250 mg/day, and half of them reported dose-limiting toxicities. There were two cases of liver damage and one case of severe fatigue and diarrhea.
Based on these findings, the lower 200 mg dose has been selected for further testing in the Phase 2 portion of the trial, according to Cothera. Of the six patients given this dose in the Phase 1 portion, two saw a reduction in tumor size following treatment, the data showed.
We remain committed to advancing zotiraciclib into subsequent phases of development with the goal of bringing a new therapeutic option to patients with IDH-mutant recurrent high-grade gliomas.
“We are grateful to the patients and families who participated in these studies, as well as to our clinical and research teams at the NCI,” said Jing Wu, MD, PhD, acting deputy chief of the neuro-oncology branch at NCI and principal investigator of the Phase 1/2 study.
“The monotherapy study data gathered to date provide important insights into the safety and biological activity of zotiraciclib,” Wu said. “We remain committed to advancing zotiraciclib into subsequent phases of development with the goal of bringing a new therapeutic option to patients with IDH-mutant recurrent high-grade gliomas.”
About the Author
