Zotiraciclib Plus Temozolomide Shows Early PFS Benefit in Recurrent Gliomas

The investigational, potent, oral CDK9 inhibitor, zotiraciclib (ZTR/TG02) in combination with temozolomide (Temodar), demonstrated early improvement in progression-free survival (PFS) as treatment of patients with recurrent high-grade gliomas, meeting the primary end point of the phase 1B 17-C-0009 trial clinical trial (NCT02942264).

Topline results announced in a press release by the developer of zotiraciclib, Adastra Pharmaceuticals, Inc, noted a profound extension of median PFS benefit among the patients in the study who had IDH1-mutated with zotiraciclib plus temozolomide compared with those who received temozolomide alone. In addition, the phase 2 dose of zotiraciclib was determined as the drug was found to be well-tolerated in patients, addressing the co-primary end point of determination of the maximum tolerated dose.

"Because preclinical data demonstrated the ability of ZTR to inhibit CDK9, enhance apoptosis and cause mitochondrial dysfunction and ultimately ATP depletion in glioma cells, we were optimistic about this first-in-human glioma trial," said Jing Wu, MD, PhD, of National Cancer Institue (NCI) and the principal investigator of the 17-C-0009 trial, in a statement. "The data from the phase 1b trial support our initial expectations and reinforce our energies to continue to investigate ZTR as a treatment for patients with gliomas."

Full results from the study are expected to be presented by the NCI, which conducted the trial, at an upcoming medical conference and published.

"We are very grateful to our NCI colleagues, the patients, and their families for their participation in this trial. Recurrent high-grade gliomas are aggressive malignant brain tumors and remain difficult cancers to treat. Currently, available agents used for the treatment of gliomas offer little or no proven benefit; new therapeutic options are needed," said Scott Megaffin, chief executive officer, Adastra Pharmaceuticals, Inc, in a statement. "We are exceptionally encouraged by the potential of zotiraciclib as a new treatment alternative for patients with recurrent high-grade gliomas. On the basis of these findings, Adastra is in active preparation of a registration-enabling clinical study of ZTR in patients with recurrent high-grade gliomas, in addition to work now underway to expand the application of ZTR to additional solid tumors and hematologic malignancies."

In the phase 1B portion of the study, patients with recurrent gliomas received the oral combination of zotiraciclib plus temozolomide in 28-day cycles. Zotiraciclib was administered 3 days before cycle 1, and then for 4 days during every cycle. Temozolomide was administered 7 days on and 7 days off for some patients and daily for other patients. All patients in the study continued treatment until disease progression or unacceptable toxicity.

Patients were eligible to enroll in the study given they have recurrent disease proven by either histology or imaging. Enrollees were required to be 18 years of age or older with no more than 2 prior disease relapses, and they must have undergone prior standard therapy for their primary disease. The required Karnofsky performance score for enrollment was > 60%. Patients must have also had adequate bone marrow function and completed treatment for prior toxicities in order to enroll in the study.

Any patient who received or who were on current treatment with an investigational drug were ineligible for the trial, as were patients who received prior bevacizumab (Avastin). Presence of serious medical condition, laboratory abnormality, or psychiatric illness were also grounds for exclusion from the study.

_Reference:

_{Adastra Pharmaceuticals announces positive top-line data from phase 1b clinical trial of zotiraciclib in the treatment of recurrent high-grade gliomas. News release. Adastra Pharmaceuticals. January 14, 2021. Accessed January 14, 2021. https://yhoo.it/2N73RO3}