Adjuvant Treatment with VAL-083 for Patients With GBM Shows Survival Benefit

Barbara Jane O’Brien, MD

Adjuvant treatment with VAL-083 following chemoradiation with temozolomide (Temodar) in patients with glioblastoma multiforme (GBM) who have an unmethylated promoter of the MGMT gene led to improvement in survival and appeared safe compared with historic control, announced Kintara Therapeutics, Inc, in a press release.

VAL-083 is a bi-functional DNA-targeting agent which preclinically demonstrated activity against multiple solid and hematologic tumors, including brain, cervical, and ovarian. The agent was granted orphan drug designations by the FDA for the treatment of GBM, medulloblastoma, and ovarian cancer. VAL-083 also has a fast track designation form the FDA for the treatment of recurrent GBM. The agent has also made regulatory progress in the European union and China.

"I continue to be impressed by the clinical data generated by both arms of the study and remain excited by VAL-083's potential to be a game-changing therapeutic agent to help patients suffering from this deadly disease, said Barbara Jane O’Brien, MD, assistant professor of neuro-oncology at The University of Texas MD Anderson Cancer Center, in the press release.

In the phase 2 study VAL-083 treatment for MGMT unmethylated bevacizumab (Avastin)-naïve GBM in the adjuvant setting, patients in the experimental group are given VAL-083 at 30 mg/m2 via intravenous infusion for 3 consecutive days at the beginning of every 21-day cycle, which is continued for 12 doses or until study discontinuation.

The primary end point of the study is overall survival (OS), and the secondary end points included estimates of progression-free survival (PFS), median PFS, OS, overall response rate, duration of response, safety, quality of life and pharmacokinetics.

The results showed that in 36 efficacy evaluable patients, the PFS was 10.0 months (95% CI, 8.2-19.8 months compared with the OFS range of 5.3 months to 6.9 months historically observed in this patient population. The median OS with VAL-083 was 16.5 months (95% CI, 13.3-19.3) compared with the historic OS of between 12.7 months and 16.0 months.

Safety findings in the phase 2 study were consistent with prior studies of VAL-083. The most common adverse event (AE) was myelosuppression, and only 2 patients had a serious AE.

Analyses are ongoing in the study, and recruitment has stopped. The study population consists of patients aged 18 years or older with a histologically confirmed diagnosis of grade IV GBM who have a Karnofsky performance status > 60%. All patients were required to have recovered from surgery and any toxicities prior to joining the study. Patients were also required to have a life expectancy of at least 12 month, and adequate bone marrow and organ function. Those in group must not have had recurrent disease, be < 6 weeks from radiotherapy before starting treatment on VAL-083 and must not have received a prior investigational agent.

“The topline results from the newly-diagnosed adjuvant arm are a particularly important milestone for the company as it further affirms the efficacy and safety data reported this past July from the recurrent arm, thus providing additional support and momentum to continue the evaluation of VAL-083 for the treatment of GBM,” said Saiid Zarrabian, chief executive officer of Kintara Therapuetics, in a press release.

^References:

^{1. Kintara Reports topline results from phase 2 clinical study of VAL-083 as adjuvant therapy for newly-diagnosed GBM patients. News release. Kintara Therapeutics, Inc. September 22, 2021. Accessed September 22, 2021. https://bit.ly/3u5IcqK}

^{2. O’Brien BJ, Kamiya-Matsuoka C, Weathers SP, et al. Abstract CT272: Phase 2 study of dianhydrogalactitol (VAL-083) in patients with MGMT-unmethylated, bevacizumab-naïve glioblastoma in the recurrent or adjuvant setting. Presented at the AACR Annual Meeting 2020; pril 27-28, 2020 and June 22-24, 2020; Philadelphia, PA. Abstract CT272.}

^{3. Study of VAL-083 in patients with MGMT unmethylated, bevacizumab-naive glioblastoma in the adjuvant or recurrent setting. Clinicaltrials.gov. Accessed September 23, 2021.}