Kintara Therapeutics announced interim data on its two Phase 2 trials of VAL-083 for the treatment of glioblastoma multiforme (GBM). The data are to be presented in two posters at the 25th Annual Scientific Meeting of the Society for Neuro-Oncology (SNO) which will be held virtually due to the Covid-19 pandemic on November 19-21, 2020.
The first poster outlined interim data from two groups of patients receiving VAL-083 in an open-label, Phase 2 study in recurrent and adjuvant unmethylated GBM settings being conducted at the MD Anderson Cancer Center in Houston.
In newly-diagnosed patients receiving VAL-083 as adjuvant therapy following treatment with radiation and TMZ, for the 27 efficacy evaluable patients (of a planned up to 36 patients) as of the data cut-off of October 23, 2020, median progression-free survival (PFS) is currently 10 months. This is not a head-to-head study, however this PFS data compares favorably to historical TMZ control of 5.3 months and 6.9 months, respectively.
For patients in the recurrent group receiving second-line therapy with VAL-083 following first-line TMZ failure, 84 patients have been enrolled as of the data cut-off of October 23, 2020 with 35 patients (34 efficacy evaluable) having received an initial dose of 40 mg/m2/day and 49 (43 efficacy evaluable) having received the planned Phase 3 initial dose of 30 mg/m2/day (on days 1, 2 and 3 of a 21-day cycle). Median overall survival (mOS) for the 77 efficacy evaluable patients who have completed at least once cycle of treatment was 7.6 months. Additionally, for the 43 efficacy evaluable patients initially receiving the planned Phase 3 initial dose of 30 mg/m2/day, mOS is currently 8.5 months.
Myelosuppression was the most common adverse event with VAL-083 in both the recurrent GBM and adjuvant treatment setting. In the 30 mg/m2/day starting dose cohort three subjects have experienced a serious adverse event (SAE) possibly related to VAL-083 in the recurrent group and one patient has experienced a possibly drug-related SAE in the adjuvant group as of the relevant data cut-off dates.
The second poster outlined the open-label, Phase 2 study of VAL-083 as a first-line treatment in newly-diagnosed, unmethylated GBM patients being conducted at Sun Yat-sen University Cancer Center in China. For the 29 patients who had completed at least their first efficacy assessment as of the October 21, 2020 cut-off date, median PFS with VAL-083 is currently 9.3 months. Additionally, for the 25 patients initially receiving the treatment dose that will be carried forward in the planned pivotal Phase 3 study of 30 mg/m2/day on days 1, 2 and 3 of a 21-day cycle, median PFS was reported to be 8.7 months. While not a head-to-head study, this PFS data compares favorably to historical TMZ control of 5.3 months and 6.9 months, respectively. Multiple treatment cycles of VAL-083 at the 30 mg/m2/day dose in combination with standard radiation treatment (2 Gy/day, 5 days/week) was shown to be generally safe and well-tolerated.
VAL-083 is a first-in-class small molecule chemotherapeutic. Its unique structure provides many valuable benefits, including the targeting of DNA for its therapeutic effect and its ability to cross the blood brain barrier, critical for activity against central nervous system (CNS) tumors.
VAL-083 has been granted orphan drug designations for the treatment of GBM from both the FDA and EMA. The FDA also granted fast track designation for VAL-083 in recurrent GBM.
About Recurrent Glioblastoma multiforme
GBM is the most common and most lethal form of brain cancer. GBM affects an estimated 12,000 new patients each year in the US alone. The median survival in newly diagnosed patients with the best available treatments is 20.5 months. After diagnosis, today’s standard treatment includes surgical resection of the tumor followed by radiotherapy and chemotherapy with temozolomide (TMZ). Nearly all GBM patients relapse following first-line treatment, and those patients have a one-year survival rate of approximately 25%. The average five-year survival rate is less than 3%.