FDA Grants Orphan Drug Designation to Zotiraciclib for Treatment of Glioma


Zotiraciclib has been granted Orphan Drug Designation by the FDA for the treatment of patients with glioblastoma, according to a press release from Adastra Pharmaceuticals, Inc.

Zotiraciclib (TG02) has been granted Orphan Drug Designation by the FDA for the treatment of patients with glioma, according to a press release from Adastra Pharmaceuticals, Inc.1

The designation from the FDA was based on results from a phase Ib clinical trial (NCT02942264), evaluating zotiraciclib plus temozolomide (Temodar) for the treatment of recurrent anaplastic astrocytoma (AA) and dose-dense (DD) or metronomic (MN) glioblastoma, which is an ongoing study sponsored by the National Cancer Institute (NCI) and led by principal investigator, Jing Wu, MD, PhD, tenure track Investigator in the Neuro-Oncology Branch at the Center for Cancer Research. Data from this study were recently presented at the 2019 Society for NeuroOncology (SNO) Meeting for patients in the trial with astrocytoma. Zotiraciclib was also granted Orphan Drug Designation recently by the European Medicines Agency (EMA).

Dose-limiting toxicities (DLT) were observed at 250 mg of zotiraciclib in 3 out of 12 patients in the group of patients with astrocytoma. The events described for this dose level were grade 4 neutropenia, grade 3 alanine transaminase elevation, and grade 3 fatigue. At 200 mg of zotiraciclib, 1 patient out of 6 experienced a DLT, which was described as grade 3 diarrhea.2

“Glioblastoma is one of the most devastating and difficult-to-treat cancers. Current therapies have limited efficacy and patient prognoses are poor, necessitating the development of new treatments with unique mechanisms of action,” Emilie Le Rhun, PhD, senior neuro-oncologist at the Department of Neurosurgery at the University Hospital Lille, France toldTargeted Oncology. “Though still early, data from the ongoing clinical trials of zotiraciclib have been encouraging and are suggestive of a therapy that is safe and capable of eliciting clinical benefit in high grade gliomas. As a uniquely differentiated CDK9 inhibitor for patients with high grade glioma, Orphan Drug Designation is another important step in the overall development process.” Le Rhun is the principal investigator for the Phase 1b trial of zotiraciclib being conducted by the European Organisation for Research and Treatment of Cancer. 

The primary end point of the phase Ib study was the MTD of zotiraciclib plus temozolomide, with a time frame of 4 weeks after initiation of treatment. The 2 study arms consisted of patients with DD or MN glioblastoma. In addition to finding the MTD, the study investigators also sought to carry out a cohort extension, which would take patients from the best responding arm and add them to a phase II study evaluating pharmacokinetics, pharmacogenetics, and performing a neutrophil analysis.

Participants in the study were given dose-escalation of zotiraciclib, starting at 200 mg for a 28-day cycle. Patients also received temozolomide starting at 125 mg in the DD arm and 50 mg in the MN arm, for a 28-day cycle.

Adults aged 18 years or older were eligible to enroll if they had a brain tumor that had progressed after standard treatment. Medical history, physical exam, blood and urine tests, MRIs of the brain, heart tests, and tissue samples from prior surgeries were all part of the screening process for the study. These patients were also required to have a Karnofsky performance status > 60%.

The study excluded individuals who were receiving treatment with investigational agents had prior treatment with bevacizumab (Avastin), and those with serious medical conditions. Laboratory abnormalities, psychiatric illnesses, history of other cancers excluded, and patients with prolonged QTc were also included in the exclusion criteria.

“We greatly look forward to reporting top-line data from the NCI Phase Ib study in early 2020, as well as completing enrollment in 2 of the European Organisation for Research and Treatment of Cancer study cohorts later in the year,” Scott Megaffin, chief executive officer of Adastra Pharmaceuticals stated in the press release.


  1. Adastra Pharmaceuticals Announces FDA and EMA Orphan Drug Designation Has Been Granted for Zotiraciclib in the Treatment of Glioma [press release]. Princeton, NJ: Adastra Pharmaceuticals, Inc.; December 4, 2019. https://prn.to/2qDEnNi. Accessed December 10, 2019.
  2. Wu J, Bryla C, Su Y, et al. Phase I trial of TG02 plus dose-dense or metronomic temozolomide for recurrent anaplastic astrocytoma and glioblastoma in adults.Neuro-Oncology. 2019;21(suppl 6; abstr ACTR-62). doi: 10.1093/neuonc/noz175.104.
Related Videos
Related Content