DelMar announced the completion of the first site initiation visit at the Dent Neurological Institute for its pivotal Phase 3 Study in Temozolomide-Avastin (bevacizumab) Recurrent GBM ("STAR-3"). Site initiation visits are generally the final step before patient enrollment.
The STAR-3 GBM trial is an adaptive design, randomized, controlled pivotal Phase 3 clinical trial to assess the efficacy and safety of VAL-083 versus salvage therapy in patients with late-stage glioblastoma multiforme (GBM) whose disease has progressed following prior treatment with temozolomide and bevacizumab, for whom there is currently no standard-of-care therapy.
The Dent Neurological Institute is the largest private neurology center in North America seeing more than 250,000 patients annually. Dr. Laszlo Mechtler will serve as principal investigator for the STAR-3 trial at Dent. Mechtler is Medical Director of Dent Neurologic Institute as well as the Chief of Neuro-Oncology at Roswell Park Cancer Institute in Buffalo, NY. He has contributed to numerous publications and is currently the Principle Investigator of multiple clinical research protocols related to Neuro-Oncology. DelMar anticipates the initiation of additional centers and commencement of treatment under the STAR-3 protocol in the coming weeks.
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" 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.
The primary endpoint of the trial is overall survival of VAL-083 vs. the control arm. 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. A detailed description of the STAR-3 trial can be found at clinicaltrials.gov, Identifier Number: NCT03149575.
"The activation of the STAR-3 trial and initiation of recruitment in collaboration with Dr. Mechtler and his team at Dent is a momentous occasion for our Company, and for the patients and their families who we hope will benefit from VAL-083," commented Jeffrey Bacha, chief executive officer of DelMar Pharmaceuticals. "In particular, GBM is a type of cancer that has been devoid of new drug approvals improving overall survival for decades, which is why we believe that VAL-083 represents tremendous value in the oncology treatment market. We are pleased to be launching this pivotal study to validate VAL-083's potential by meeting the objectives in the STAR-3 trial."
VAL-083 (dianhydrogalactitol) is a "first-in-class", DNA-targeting agent that introduces interstrand DNA cross-links at the N7-position of guanine leading to DNA double-strand breaks and cancer cell death. VAL-083 has demonstrated clinical activity against a range of cancers including GBM in historical clinical trials sponsored by the U.S. National Cancer Institutes.
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.
The company'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.