By Grant Zeng, CFA
DMPI Begins Dosing of Patients in Phase II Trial of VAL-083 for MGMT-unmethylated Recurrent Glioblastoma Multiforme
On Feb. 13, 2017, DMPI (NASDAQ:DMPI) announced that it has commenced dosing patients in a Phase II clinical study of VAL-083 (dianhydrogalactitol) for MGMT-unmethylated Avastin®(bevacizumab)-naïve recurrent glioblastoma. The study is currently enrollin patients at the University of Texas MD Anderson Cancer Center.
- The single arm, biomarker-driven Phase II trial (NCT02717962) will test safety, tolerability and clinical efficacy of VAL-083 in 48 adult subjects with MGMT-unmethylated GBM whose tumors have recurred following surgery and standard chemo-radiation with temozolomide.
- Patients will receive 40 mg/m2 VAL-083 (IV) on days 1, 2, and 3 of a 21-day treatment-cycle, for up to twelve 21-day treatment cycles to determine if treatment with VAL-083 improves overall survival compared to historical controls.
- The lomustine arm of the recently published EORTC26101 trial will serve as the reference control;
The majority of newly diagnosed GBM patients' tumors are characterized as MGMT-unmethylated, which is directly correlated with resistance to current standard front-line chemoradiation with temozolomide. VAL-083 is independent of MGMT expression and may provide a new therapeutic option for GBM patients whose tumors exhibit features making them resistant or unlikely to respond to currently available therapy.
Two New Clinical Trials with VAL-083 Will be Initiated Soon
A pivotal, randomized multi-center Phase III study measuring survival outcomes compared to a "physicians' choice" control for the treatment of bevacizumab-failed GBM
In late May 2016, DelMar announced the successful completion of an End of Phase II meeting with the FDA.
The FDA confirmed that it will consider the totality of data available, including data obtained from DelMar's other planned clinical trials in related GBM populations, when assessing the NDA. The FDA also noted that DelMar can rely on prior US National Cancer Institutes (NCI) studies and historical literature to support non-clinical data required for an NDA filing and that DelMar will have the option to file under a 505(b)(2) strategy, which allows a sponsor to rely on already established safety and efficacy data in support an NDA.
A summary of the proposed clinical trial design includes:
- Approximately 180 patients with histologically confirmed recurrent GBM who have failed both standard chemo-radiation and bevacizumab will be randomized in a 2:1 fashion to receive either VAL-083 or a commonly used salvage chemotherapy;
- The proposed study is projected to be enrolled at approximately 25 centers;
- The proposed primary endpoint is overall survival (OS);
- The proposed 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; and
- The estimated length of the proposed study is less than two years from initiation.
The proposed trial design is subject to feedback from the FDA and other regulatory authorities. DelMar plans to submit the protocol to the FDA in coming weeks.
An open label, single-arm, biomarker-driven, Phase II study of VAL-083 and radiation therapy patients in newly diagnosed MGMT-unmethylated GBM
- This single-arm trial will enroll up to 30 newly diagnosed (temozolomide-naïve) GBM patients to examine whether VAL-083 is active in patients with newly diagnosed GBM with MGMT-unmethylated compared to historical control;
- If successful, data from the trial will serve as a lead-in to a global randomized Phase II/III clinical trial of VAL-083 in newly diagnosed GBM patients with MGMT-unmethylated;
- Progression free survival (PFS) will serve as the primary endpoint to assess VAL-083 treatment activity;
- The study will also confirm the safety and tolerability of VAL-083 in combination with a standard-of-care radiation regimen; and
- The study will initially be enrolled at the Sun-Yat Sen University (Guangzhou, China) as a single center trial, but may be expanded to include additional centers.
This trial is being conducted in collaboration with Guangxi Wuzhou Pharmaceutical (Group) Co. Under the terms of the company's collaboration agreement Guangxi Wuzhou Pharmaceuticals is providing drug product and funding for the trial. The Sun-Yat Sen University Clinical Review Committee has approved the protocol and DelMar is completing the final remaining regulatory steps required for initiation of the trial and expects to begin enrollment in 1H2017.
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