– 60% overall response rate; 96% achieved stable disease or better –
– 12.9 mo. median and 60% 1-year overall survival in combination with Avastin® –
– Safety profile remains favorable; no dose-limiting toxicities to date –
CHICAGO, June 03, 2016 (GLOBE NEWSWIRE) -- Cortice Biosciences announced today updated results from CB-017, a Phase 1/2 clinical trial evaluating TPI 287 plus bevacizumab (Avastin®) in patients with recurrent glioblastoma (GBM) who have not received prior bevacizumab. These results will be presented tomorrow during a poster session at the 2016 American Society of Clinical Oncology Annual Meeting (Abstract #2055).
“Since last November, data from our TPI 287 development program continues to support meaningful drug activity in GBM,” said George Farmer, Ph.D., Chief Executive Officer of Cortice. “Compared to the 7-9 month median overall survival observed in landmark clinical trials evaluating other treatment combinations with bevacizumab, outcomes in CB-017 are very encouraging. We look forward to presenting final results from the Phase 1 portion of the study later this year.”
TPI 287 is a novel microtubule stabilizing agent that readily penetrates the blood-brain barrier. Prior preclinical and clinical results support the potential of this agent for the treatment of aggressive brain cancers in patients with few therapeutic options.
Results in detail
Twenty-four patients with recurrent GBM that had progressed beyond first line treatment and who had not received prior bevacizumab were enrolled in the dose-escalation portion of CB-017. In addition to TPI 287 (140 to 220 mg/m2 administered every three weeks in seven dose cohorts), all patients received standard-of-care bevacizumab (10 mg/kg every two weeks). Twenty and 23 patients were evaluable for overall response and overall survival, respectively.
Key efficacy metrics are as follows:
- Overall response
- As previously reported, 12 patients achieved an objective response per RANO criteria, including 3 complete (CR) and 9 partial (PR) responses. This corresponds to a 60% overall response rate.
- Ten patients achieved stable disease (SD) and 1 patient had progressive disease at first assessment for response. This corresponds to a 96% disease control rate (CR + PR + SD).
- Survival
- Final median progression free survival from this portion of the study is 5.5 months [95% C.I. 4.1, 8.2].
- To date, median overall survival is 12.9 months [95% C.I. 10.9, 17.9] after the occurrence of 74% of possible events and a median follow-up of 20.2 months.
- Of 20 patients with sufficient follow-up, 12 (60%) were or have been alive for at least 1 year.
Safety data available from 22 patients enrolled in CB-017 continues to support the favorable tolerability profile of TPI 287. With the exception of Grade 3 myelosuppression (3 patients), all adverse events regarded as possibly related to TPI 287 have been mild to moderate. No dose limiting toxicities (DLTs) have been observed to date.
Based on observations from the dose-escalation portion of CB-017, an optimal dose of TPI 287 has been selected for the expansion stage of the trial. Following guidance recently provided by FDA, results from this study will inform the design of a single Phase 3 registration trial for TPI 287 in GBM.
“The positive survival trend and excellent tolerability of TPI 287 observed in the Phase 1 portion of our study support continued investigation in glioblastoma,” said Dr. Samuel Goldlust, Medical Director of the Brain and Spine Institute of the John Theurer Cancer Center in Hackensack, NJ and Principal Investigator of CB-017. “With no current treatment options known to extend survival at recurrence, our patients are in desperate need of new therapies.”
About TPI 287
TPI 287 is a novel taxoid which binds to and stabilizes the assembly of microtubules similarly to commonly used taxanes, including paclitaxel (Taxol® and Abraxane®) and docetaxel (Taxotere®). In oncology treatment settings, microtubule stabilization by these agents leads to mitotic arrest and cancer cell death. TPI 287 has advantages over these taxanes due to its ability to circumvent common drug resistance mechanisms and its propensity to penetrate the central nervous system. Accordingly, TPI 287 has the potential to treat primary brain tumors and secondary brain metastases that are often shielded from systemic administration of taxanes and other chemotherapeutics. Microtubule stabilization by TPI 287 may also have potential for the treatment of neurologic disorders affected by tau protein pathology. These include tauopathies such as Alzheimer’s disease and orphan diseases, such as progressive supranuclear palsy, corticobasal degeneration, and frontotemporal dementia.
About Glioblastoma
Glioblastoma (GBM) is the most aggressive and common form of brain cancer. Five-year survival after diagnosis is about 5%. The Central Brain Tumor Registry estimates that about 24,790 primary malignant brain tumors cases will be diagnosed in the US in 2016, 46% of which will be GBM. Typical front-line treatments include stereotactic or whole brain radiotherapy plus temozolomide (Temodar®). Patients with recurrent disease are candidates for treatment with Avastin®, the last FDA approved agent for this disease.
About Cortice Biosciences
Cortice Biosciences, Inc. is a clinical-stage drug development company developing novel therapies for oncologic and neurologic disease indications with urgent unmet medical need. More information can be found at www.corticebiosciences.com.
Safe Harbor Statement
This media release may contain forward-looking statements about Cortice Biosciences, which can be identified by the use of terminology such as "will," "would," "should," "expects," "anticipates," "intends," "plans," "believes," "may," "estimates," "predicts," "projects,” or similar expressions intended to identify such statements. These statements reflect the current views of Cortice with respect to future events, are based on assumptions, and subject to risks and uncertainties.