DelMar’s New Chemotherapeutic VAL-083 Shows Promise in TKI-resistant NSCLC

DelMar’s New Chemotherapeutic VAL-083 Shows Promise in TKI-resistant NSCLC

DelMar‘s small molecule chemotherapeutic VAL-083 may be a valuable treatment approach for non-small cell lung cancer (NSCLC) patients who are resistant to tyrosine kinase therapy, according to preclinical data presented at the American Association for Cancer Research (AACR) 2017 Annual Meeting in Washington, D.C.

The poster, “DNA damage response to dianhydrogalactitol (VAL-083) in p53-deficient non-small cell lung cancer (NSCLC) cells,” was presented April 3 by Anne Steino.

Treatment of non-small cell lung cancer patients who have EGFR mutations usually consists of surgery and chemotherapy with tyrosine kinase inhibitors (TKI). EGFR mutations are found in nearly 15% of NSCLC patients in the Western population, and 40% in Asian populations.

While TKI therapy has shown promise in lung cancer patients, response to TKI treatment is short-lived and tumors recur with new mutations, like the T790M EGFR mutation.

And while recurrent NSCLC with the T790M mutation is sensitive to third-generation TKIs, resistance usually emerges through new mutations, including KRAS mutations.

VAL-083 is a first-in-class, small molecule DNA-targeting chemotherapy. It is approved in China for the treatment of chronic myelogenous leukemia and lung cancer, but its use has been limited by a lack of new data.

But recent findings from DelMar researchers suggest that VAL-083 has the potential to exert high anti-cancer activity, even in NSCLC cells that are highly resistant to platinum-based chemotherapy, the standard-of-care for non-operable NSCLC.

In addition, VAL-083 readily crosses the blood brain barrier, and may possibly be used to treat patients whose lung cancer has spread to the brain.

The recently presented data has demonstrated that VAL-083 also retains its anti-tumor activity in NSCLC cells that acquired resistance to TKI therapies. Indeed, cells with p53, EGFR, or KRAS mutations were highly sensitive to the drug.

The preclinical results provide the scientific rationale for further assessement of VAL-083 in NSCLC clinical trials, and the company says on its website that it has plans to initiate a NSCLC trial in collaboration with Guangxi Wuzhou Pharma, which will fund the study.

The company presented two other posters, showing the mechanism of action of VAL-083 in glioblastoma and data from a Phase 2 trial in MGMT expressing glioblastoma tumors.

VAL-083 has received orphan drug designation in Europe to treat malignant gliomas, and in the U.S. for the treatment of glioma, medulloblastoma, and ovarian cancer.

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