VAL-083 in combination with radiotherapy appears safe and active in patients with newly diagnosed MGMT-unmethylated glioblastoma, according to research presented in a poster at the Society for Neuro-Oncology 27th Annual Meeting.
Progression-free survival (PFS) and overall survival (OS) results with VAL-083 plus radiotherapy were similar to PFS and OS results previously observed with temozolomide, researchers reported.
“VAL-083 is a novel bi-functional DNA targeting agent that induces inter-strand DNA cross-links at N7-guanine, leading to DNA double-strand breaks and cell death,” the researchers explained.
They conducted a phase 2 trial (ClinicalTrials.gov Identifier: NCT03050736) to evaluate VAL-083 given concurrently with radiotherapy in patients with newly diagnosed MGMT-unmethylated glioblastoma.
In the dose-escalation phase of the study, patients received VAL-083 at 20 mg/m2, 30 mg/m2, or 40 mg/m2 per day for 3 days every 21 days, in combination with standard radiotherapy (2 Gy per day, 5 days per week). In the expansion phase, patients received standard radiotherapy and VAL-083 at 30 mg/m2.
Patients received VAL-083 plus radiotherapy for 6 weeks, followed by up to 8 weeks of maintenance with VAL-083 alone.
Of the 29 total patients, 18 (62.1%) completed at least 8 cycles of treatment, and 14 (48.3%) completed at least 10 cycles of treatment. The median number of completed treatment cycles was 9 (range, 2-13) for the 25 patients who received VAL-083 at 30 mg/m2.
In the overall cohort, the most common adverse events (AEs) were myelosuppression and anemia, but hematologic AEs generally resolved spontaneously, according to the researchers. There were 3 serious AEs possibly related to VAL-083 — 2 cases of thrombocytopenia and 1 liver disorder.
For all 29 patients, the median PFS was 9.3 months, and the median OS was 19.6 months. Eighteen of the patients ultimately died (62.1%).
Among the 25 patients treated with VAL-083 at 30 mg/m2, the median PFS was 8.7 months, which was numerically higher than the 5.3 months seen in historical reference data for temozolomide.
The median OS among patients who received VAL-083 at 30 mg/m2 was also numerically higher than the historical reference — 19.1 months and 12.7 months, respectively.
The researchers concluded that VAL-083 at 30 mg/m2 in combination with radiotherapy is “generally safe and well-tolerated,” and the combination “demonstrated benefit over historical standard-of-care temozolimide in the same setting.”
Disclosures: This research was supported by Kintara Therapeutics, Inc. Some of the poster authors are employed by the company.
Chen Z, Guo C, Chen J, et al. Phase 2 study of VAL-083 and radiotherapy in newly diagnosed MGMT-unmethylated GBM. Presented at SNO 2022; November 16-20, 2022. Abstract CTNI-32.