US-based clinical-stage drug development firm Cortice Biosciences has started the first stage of an open-label Phase II trial designed to assess the safety and efficacy of its lead drug candidate, TPI 287, in combination with standard-of-care Avastin (bevacizumab) for treatment of patients with recurrent glioblastoma (GBM) that has progressed after Avastin treatment alone.
TPI 287 is a novel taxoid derivative, known as an abeotaxane, which binds to and stabilises the assembly of microtubules similar to commonly used taxanes, including paclitaxel (Taxol and Abraxane) and docetaxel (Taxotere).
It has distinct advantages of being able to readily cross the blood-brain barrier and evade common drug resistance mechanisms.
The first stage of the trial is designed to determine the maximum tolerated dose (MTD) of TPI 287 given every three weeks when used in combination with Avastin administered at 10mg/m² every two weeks.
The company said that all patients will have GBM that has progressed while on or following treatment with Avastin.
Following the establishment of MTD for TPI 287 in this setting, the company intends to expand to the second stage of the trial to assess additional patients with TPI 287 plus Avastin.
The primary endpoint of the trial is safety, while major secondary endpoints include overall response rate and progression-free survival, and will be assessed per RANO criteria.
Previous experience with TPI 287 in recurrent GBM patients indicates that the drug may have meaningful impact on treating infiltrative disease, which often evades Avastin therapy; therefore, TPI 287 and Avastin may be synergistic as treatment for recurrent GBM.
In order to investigate the potential synergy, the company is carrying out a separate clinical trial to assess TPI 287 in combination with Avastin for treatment of recurrent GBM naive to prior Avastin treatment.
University of Alabama director of the Division of Neuro-Oncology Dr Burt Nabors said the organisation is happy to be part of the clinical trial evaluating TPI 287 in recurrent GBM, a disease with very few effective treatment options.
"Results from this trial, as well as Cortice's other Phase II trial evaluating TPI 287 in patients naive to bevacizumab, could be informative and instrumental in bringing a new therapy to our patients," Dr Nabors said.
Image: Histopathological image of cerebral glioblastoma. Photo courtesy of KGH.