February 26, 2014
DelMar Pharmaceuticals, Inc. provided an update on the company’s ongoing Phase I/II clinical trial for VAL-083 in recurrent glioblastoma (GBM).
DelMar has completed enrolment of VAL-083 dose Cohort 5 and advanced to Cohort 6.
DelMar most recently presented VAL-083 interim clinical data in November 2013 at the 18th Annual Society for NeuroOncology (SNO) meeting. At that time, it was announced that enrollment of Cohort 5 (20mg/m2) was expected to commence in December 2013, subject to completion of the mandated safety observation period for Cohort 4 (10mg/m2).
Enrollment of Cohort 5, including a mandatory safety observation period, has been completed. VAL-083 was well tolerated by patients treated in the study with no significant adverse events or dose limiting toxicity (DLT) reached. The maximum tolerated dose (MTD) for VAL-083 has not yet been achieved. While clinical observations of Cohort 5 are ongoing, the Company has now begun enrollment for Cohort 6 (30mg/m2).
DelMar is on track to deliver higher doses of VAL-083 than have been used in prior clinical studies.
Previous VAL-083 clinical trials sponsored by the National Cancer Institute (NCI) reported promising safety and efficacy data for the treatment of GBM. Going forward, the DelMar clinical trial will be delivering higher doses of VAL-083 more often in comparison to the historical GBM treatment regimen studied at the NCI. The NCI-sponsored studies, a cumulative dose of 125mg/m2 delivered in a 33 day cycle in combination with radiation was demonstrated to be superior to radiation alone (Eagan et al. 1979). In a comparative 33-day cycle, Cohort 6 of DelMar’s dosing regimen will deliver a total of 180/mg2taking advantage of higher drug concentration and exposure to the tumor.
“Reaching the 30mg/m2 dose cohort is an important clinical milestone in the development of VAL-083 as a potential treatment for refractory GBM,” said Jeffrey Bacha, president & CEO of DelMar Pharmaceuticals. “We are hopeful that our strategy of taking advantage of a higher concentration and higher exposure in comparison to the NCI regimen will enable us to build upon the experience of previous NCI-sponsored studies and position VAL-083 as a promising new treatment option for GBM patients who have failed other available therapies.”
Interim clinical data from the ongoing dose escalation study will be presented at the American Association of Cancer Research (AACR) Annual Meeting on April 9, 2014.
DelMar will present updated interim clinical data, including available data from Cohort 6, at the upcoming American Association of Cancer Research (AACR) Annual Meeting, which is being held April 5 – 9 in San Diego, CA. Details of the company’s abstract presentation can be found here, or by searching permanent abstract #CT404 at www.aacr.org.
VAL-083 represents a first-in-class, small-molecule chemotherapeutic with a unique mechanism of action. In more than 40 Phase 1 and 2 clinical studies sponsored by the National Cancer Institute (NCI), VAL-083 demonstrated promising activity against a number of cancers including lung, brain, cervical, ovarian tumors and leukemia. VAL-083 is approved in China for the treatment of chronic myelogenous leukemia and lung cancer and has received orphan drug designation in Europe and the U.S. for the treatment of gliomas. DelMar previously presented in vitro data demonstrating that VAL-083’s unique mechanism of action is unaffected by the expression of MGMT, a DNA repair enzyme that causes chemotherapy resistance to Temodar® (temozolomide). Temodar is currently the standard front-line therapy for the treatment of glioblastoma multiforme (GBM), the most common and aggressive form of brain cancer. DelMar believes that these data, in conjunction with VAL-083’s historical activity, establish the drug’s potential to provide a viable treatment option for patients suffering from refractory and newly-diagnosed GBM.
About the Phase I/II VAL-083 Dose Escalation Trial
DelMar’s Phase I/II study is an open-label, single arm dose-escalation study designed to evaluate the safety, tolerability, pharmacokinetics and anti-tumor activity of VAL-083 in patients with recurrent GBM. Patients in the trial must have been previously treated for GBM with surgery and/or radiation and must have failed both Avastin® and Temodar®, unless either or both are contra-indicated. Subject to continued progress, DelMar anticipates completing the dose-escalation portion of its current clinical trial in mid-2014. The goal of the dose-escalation portion of the trial is to determine an appropriate dosing regimen for advancement into future registration-directed trials.
Read more here.