VANCOUVER, British Columbia and MENLO PARK, Calif., June 22, 2017 /PRNewswire/ — DelMar Pharmaceuticals (Nasdaq: DMPI) (“DelMar” and “the Company”), a biopharmaceutical company focused on the development of new cancer therapies, today announced it has received Institutional Review Board (IRB) approval to conduct its pivotal Phase 3 Study in Temozolomide-Avastin (bevacizumab) Recurrent GBM (STAR-3).
“IRB approval is an essential step in initiating patient enrollment in our Phase 3 trial,” stated Jeffrey Bacha DelMar’s chairman & CEO. “We are pleased to remain on track to open enrollment in this trial at leading centers in the United States. Based on our research, we believe that VAL-083 offers significant potential as a new therapy for GBM patients who currently have no viable treatment options.”
Under FDA regulations, Institutions Review Boards (IRBs) are required to review all human subject research to ensure that the rights and welfare of human subjects are protected at all times. To accomplish this purpose, IRBs are comprised of physicians and research administrators with the authority to approve, require modifications to, or disapprove research. The VAL-083 STAR-3 GBM trial and all pertinent study related materials were critically examined by Schulman IRB, the leading independent institutional review board, and approved without any modifications.
A total of up to 180 eligible patients will be randomized at approximately 25 centers in the United States to receive either the investigational drug (VAL-083) or “investigator’s choice salvage therapy” as a contemporaneous control, in a 2:1 fashion. Up to 120 eligible patients will be randomized to receive intravenous VAL-083 at 40 mg/m2 on days 1, 2, and 3 of a 21-day treatment cycle, for up to 12, 21-day treatment cycles or until they fulfill one of the criteria for study discontinuation. Up to 60 patients will be randomized to “investigator’s choice” control, limited to temozolomide, lomustine, or carboplatin, until they fulfill one of the criteria for study discontinuation.
In both study arms, interval medical histories, targeted physical exams, neurologic evaluations, complete blood counts, and other laboratory and safety assessments will be performed approximately every 21 days while receiving treatment. Tumor assessments are to be performed approximately every 42 ± 7 days while remaining on study. The study is estimated to last less than two years from initiation.
The primary endpoint of the trial is overall survival. The statistical design between the two arms of the study is 90% power, and is proposed to include an interim analysis at 50% events for futility with O’Brien-Fleming superiority boundary and non-binding, gamma (-5) futility boundary.
VAL-083 has been granted an orphan drug designation by the U.S. FDA Office of Orphan Products for the treatment of glioma, medulloblastoma and ovarian cancer, and in Europe for the treatment of malignant gliomas.
DelMar has demonstrated that VAL-083’s anti-tumor activity against GBM is unaffected by the expression of MGMT in vitro. Further details regarding these studies can be found at http://www.delmarpharma.com/scientific-publications.html.
DelMar’s recent outcomes in Phase 1-2 clinical trials suggested that VAL-083 may offer a clinically meaningful survival benefit for patients with recurrent GBM following treatment with both TMZ and bevacizumab. A well-tolerated dosing regimen of 40mg/m2/day on days 1, 2, and 3 of a 21-day cycle was selected for study in subsequent GBM clinical trials.
DelMar has embarked human clinical trials for VAL-083 across multiple lines of GBM therapy. These trials include, i) an ongoing single-arm, biomarker driven, Phase 2 study to determine if VAL-083 treatment of MGMT-unmethylated adult GBM patients at first recurrence/progression, prior to bevacizumab, improves overall survival, compared to historical control with lomustine (clinicaltrials.gov identifier: NCT02717962); ii) a pivotal, controlled Phase 3 study in temozolomide-Avastin Recurrent GBM (“STAR-3”) to evaluate overall survival versus salvage chemotherapy (clinicaltrials.gov identifier: NCT03149575); iii) a single arm, biomarker driven, Phase 2 study to confirm the tolerability and efficacy of VAL-083 in combination with radiotherapy in newly diagnosed MGMT-unmethylated GBM patients whose tumors are known to express high MGMT levels (clinicaltrials.gov identifier: NCT03050736). The results of these studies may support a new treatment paradigm in chemotherapeutic regimens for the treatment of GBM.