Phase III Trial of First-in-Class Chemotherapeutic Enrolls Patients Following Positive Data Presented at SNO

A phase III clinical trial of VAL-083, a first-in-class small molecule chemotherapy agent, has opened for patients with glioblastoma multiforme whose disease has progressed during or after standard treatment with chemoradiation, according to a news release from Atlantic Health System.  

Kurt Jaeckle, MD

A phase III clinical trial of VAL-083, a first-in-class small molecule chemotherapy agent, has opened for patients with glioblastoma multiforme (GBM) whose disease has progressed during or after standard treatment with chemoradiation, according to a news release from Atlantic Health System.

“The availability of this and other neuro-oncology clinical trials provides a benefit to our patients, and gives me hope for the future,” Kurt Jaeckle, MD, co-director of the Gerald J. Glasser Brain Tumor Center of Overlook Medical Center, who will be leading the trial at this location, said in a statement.

The phase III trial is a randomized, controlled study with an adaptive design and is enrolling adult patients with GBM or gliosarcoma who have previously been treated with chemoradiation of temozolomide (Temodar) with or without adjuvant temozolomide and bevacizumab (Avastin), and surgery, if appropriate. The trial is expected to enroll up to 180 eligible patients who will be randomized 2:1 to either 40 mg/m2intravenous VAL-083 on days 1, 2, and 3 of a 21-day cycle for up to 12 cycles, or investigator’s choice of salvage therapy including temozolomide, lomustine, or carboplatin.

Patients are being recruited at 4 sites: the Gerald J. Glasser Brain Tumor Center; Kaiser Permanente Los Angeles Medical Center; University of California, San Francisco (UCSF); and Dent Neurosciences Research Center.

“Glioblastoma is very difficult to treat, and I am encouraged by previously reported results with VAL-083,” said Jaeckle.

In findings from 2 single-arm phase II trials of VAL-083 in patients with MGMT-unmethylated GBM presented at the 2017 Society of Neuro-Oncology (SNO) Annual Meeting, investigators demonstrated the promising results for the agent. One study investigated VAL-083 in combination with radiotherapy in a newly diagnosed patient population, and the other focused on patients at first recurrence or progression of their disease who have not received prior bevacizumab in comparison with historical controls of patients treated with lomustine.

In the trial of patients with recurrent MGMT-unmethylated GBM, 27 patients were screened and 15 were enrolled. Fourteen patients (96%) were alive at the time of the analysis and 6 patients (40%) had achieved stable disease. The median overall survival had not yet been reached, and enrollment and treatment is ongoing in the study. VAL-083 was well tolerated by patients and demonstrated a safety profile similar to clinical expression, with noted cases of myelosuppression.

"The promising early observations from our ongoing Phase 2 clinical trial of VAL-083 as a potential new treatment option for MGMT-unmethylated GBM are also supported by extensive preclinical research into VAL-083's unique mechanism of action," Saiid Zarrabian, interim chief executive officer of DelMar Pharmaceutics, the company developing the chemotherapeutic, said in a statement following the presentation at the SNO meeting. "Based on these recent data, we believe VAL-083 represents a potential solution for some of the most important unmet medical needs in the treatment of GBM and other central nervous system tumors."

VAL-083 has been approved for use in the treatment of patients with chronic myelogenous leukemia and lung cancer in China.

Reference:

Bacha J, Steino A, Langlands J, et al. Clinical trials with dianhydrogalactitol (VAL-083) in MGMT-unmethylated glioblastoma.Neuro Oncol. 2017;19(suppl 6; abstr ACTR-50):vi11. doi: 10.1093/neuonc/nox168.041.