– 13.4 month median overall survival; 64% of patients alive after one year –
– 60% objective response rate; 96% disease stabilization rate –
– Clinical outcomes and biomarker data further support the therapeutic potential of TPI 287 –
CHICAGO, June 05, 2017 (GLOBE NEWSWIRE) -- Cortice Biosciences announced today final results from the dose escalation portion of CB-017, a Phase 1/2 clinical trial evaluating TPI 287 plus bevacizumab (Avastin®) in patients with recurrent glioblastoma (GBM), a highly aggressive form of brain cancer. These results will be presented this afternoon at the 2017 Annual Meeting of the American Society of Clinical Oncology (ASCO) during the Central Nervous System Tumors poster session beginning at 1:45 PM and reviewed at the corresponding discussion session beginning at 4:45 PM CDT.
TPI 287 is a novel microtubule stabilizing agent that readily penetrates the blood-brain barrier and kills rapidly dividing cancer cells. Other anti-cancer agents of the same class, including paclitaxel (Taxol®), have been shown to exhibit synergy with bevacizumab for the treatment of other solid tumor indications, but do not readily cross the blood-brain barrier. This warrants investigation of TPI 287 in recurrent GBM where single agent bevacizumab is a standard-of-care.
“The final results from the Phase 1 portion of CB-017 continue to support meaningful activity of TPI 287 in GBM,” said George Farmer, Ph.D., Chief Executive Officer of Cortice. “Comparing these results with those from other landmark recurrent GBM trials suggests that TPI 287 could be an effective add-on to bevacizumab treatment. We look forward to developing TPI 287 further with the goal of bringing a much needed new therapy to GBM patients.”
Results in detail
Twenty-four patients with GBM that had progressed beyond first line treatment and who had not received prior bevacizumab were enrolled in the Phase 1 dose-escalation portion of CB-017. In addition to TPI 287 (administered every 3 weeks in 7 dose cohorts of 140 to 220 mg/m2), 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.
- Overall response
-- Twelve of 20 evaluable 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 of 23 evaluable 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
-- Median progression free survival was 5.5 months [95% C.I. 4.1, 8.2].
-- Median overall survival was 13.4 months [95% C.I. 10.9, 17.9] after the occurrence of 87% of possible events; 14 (64%) patients were or have been alive for at least 1 year since starting therapy with TPI 287 and bevacizumab.
The methylation status of promoter sequences that drive expression of the gene encoding O(6)-methylguanine-DNA methyltransferase (MGMT) is prognostic for overall survival in GBM patients. Historically, patients harboring unmethylated MGMT promoters in tumors, who comprise about 55 to 60% of all GBM cases, tend to have shorter survival outcomes than patients harboring methylated MGMT promoter sequences in tumors.
- Of 9 patients enrolled in CB-017 from which biomarker status was available, 8 patients (89%) had tumors that harbored unmethylated MGMT promoters, suggesting that the patients enrolled in this trial had an overall worse prognosis than those of a more typical GBM population characterized by this biomarker.
- Four of 7 evaluable patients who were negative for the MGMT promoter biomarker achieved an objective response, while 3 patients had stable disease. This supports activity of TPI 287 plus bevacizumab in this relatively difficult-to-treat patient population.
Overall response rates from other trials enrolling recurrent GBM patients treated with bevacizumab alone range from 6 to 26%. Median and 1-year overall survival rates range from 7 to 9 months and 25 to 38%, respectively. Given the significantly higher response rate and overall survival outcomes observed in CB-017 as well as the MGMT promoter biomarker data, the results presented today suggest that TPI 287 plus bevacizumab is a more effective regimen than standard-of-care bevacizumab alone for treatment of this disease.
Safety data available from 22 patients in CB-017 supports 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) were observed in this study.
“These Phase 1 results support the therapeutic utility of TPI 287 for treatment of glioblastoma, the most common and aggressive primary brain cancer,” 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. “Importantly, the fact that most of the patients from whom samples were available had tumors that harbored an unmethylated MGMT promoter makes the survival results reported today even that much more impressive.”
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 for the treatment of brain cancers due to its ability to penetrate the central nervous system, which is often shielded from systemic administration of other anti-cancer drugs. 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 2017, 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 drug approved by FDA 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.
Source: Cortice Biosciences, Inc.