DelMar Pharmaceuticals announced the University of Texas MD Anderson Cancer Center's (MDACC) Institutional Review Board (IRB) has approved a trial protocol amendment to expand DelMar's ongoing Phase 2 clinical trial of VAL-083 in patients with MGMT-unmethylated glioblastoma (GBM). The biomarker driven trial, which was originally designed as a single arm study evaluating VAL-083 in patients with MGMT-unmethylated bevacizumab (Avastin)-naïve recurrent GBM, has been expanded to include an additional maintenance-stage (adjuvant therapy) treatment group.
This protocol amendment, in addition to the Company's ongoing Phase 2 trial in newly diagnosed patients with MGMT-unmethylated GBM being conducted at Sun Yat-sen University Cancer Center (SYSUCC), expands DelMar's evaluation range of VAL-083 as a potential treatment for unmethylated GBM patients to include newly-diagnosed, maintenance-stage, and recurrent patients. Maintenance-stage GBM provides the greatest opportunity to control disease progression after radiation therapy, and represents the largest addressable GBM market opportunity for VAL-083 given patients are typically healthier and as such, are able to optimally benefit therapeutically from increased treatment cycles compared to the recurrent treatment setting. Maintenance GBM patients may be able to receive 12+ cycles of VAL-083 versus 5 or 6 cycles for recurrent GBM patients.
"VAL-083 offers a unique therapeutic approach that is independent of MGMT promoter status, has been shown to be safe, and may provide a valuable treatment option for the over 60% of patients with MGMT promoter unmethylated GBM who do not currently have strong chemotherapy options. As such, we are excited to expand the ongoing clinical trial at MD Anderson Cancer Center to include up to 24 maintenance (adjuvant) stage patients in the new treatment arm. This provides trial patients with VAL-083 much earlier than in the recurrent setting, and in lieu of adjuvant therapy with TMZ, which is acknowledged to be of limited value in this patient population," said Principal Investigator Dr. Barbara O'Brian, Assistant Professor, Department of Neuro-Oncology, MD Anderson Cancer Center.
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"The MGMT-unmethylated GBM patient population represents a significant unmet medical need and in fact, the 2017 NCCN guidelines highlight the inadequacy of currently approved therapies for these patients, who represent the majority of GBM cases. As the only company with late stage clinical assets focused on this underserved patient population, we are extremely pleased with the MDACC's IRB approval to expand the Phase 2 trial to include the MGMT-unmethylated patients in the maintenance-stage setting," said Saiid Zarrabian, President and Chief Executive Officer of DelMar Pharmaceuticals. "Moving forward, we will continue to maintain our clinical development focus on this biomarker-enriched patient population while leveraging our fast track status with the FDA to optimize the path to a potential regulatory approval."
The additional maintenance-stage treatment group is expected to enroll up to 24 newly diagnosed GBM patients who have completed chemo-radiation treatment with temozolomide (TMZ) without the continued TMZ maintenance therapy as provided for on the label. The trial will determine if intervention prior to TMZ maintenance therapy offers clinical benefit and extends the time to recurrence as compared to TMZ maintenance. In addition, the protocol amendment provides for enrollment of up to 35 additional patients for the ongoing recurrent patient trial arm to enable the trial arm to maintain the originally planned statistical powering.
VAL-083 (Dianhydrogalactitol) is a novel bi-functional DNA targeting agent that rapidly induces interstrand cross-links at N7-guanine, leading to DNA double-strand breaks and ultimately cell death. VAL-083's unique cytotoxic mechanism circumvents MGMT mediated chemoresistance and differentiates it from other therapies used in the treatment of GBM, including TMZ. This makes VAL-083 an ideal candidate to explore treating patients who are unlikely to respond to TMZ due to MGMT expression in their GBM as per the 2017 National Comprehensive Cancer Network guidelines (NCCN).
VAL-083 has been granted orphan drug designations 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. VAL-083 has been granted fast-track status for the treatment of recurrent GBM by the US FDA.