AVB-500 Plus Chemotherapy More Effective Than Chemo Alone in Platinum-resistant Patients, Early Trial Data Suggest

Aravive‘s experimental treatment, AVB-500, in combination with chemotherapy appears to be more effective than chemotherapy alone at treating platinum-resistant ovarian cancer, preliminary results from a first group of patients taking part in a Phase 1b/2 trial show.

The company will increase enrollment in this U.S. study to further evaluate these early outcomes.

“We have decided to expand the clinical trial to validate that early positive efficacy signal,” Laura Bonifacio PhD, vice president of Aravive, said in a press release. “If we continue to see a robust efficacy signal, we plan to work with FDA to explore the most efficient regulatory pathway to bring this drug to the patients in need.”

AVB-500 (previously known as AVB-S6-500) binds with high affinity to a protein called growth arrest-specific factor 6 (GAS6), preventing it from interacting with the AXL receptor and inhibiting the activation of the Gas6-AXL pathway, which plays a role in cancer progression.

High levels of GAS6 in the blood are associated with more aggressive cancer, resistance to treatment, and poorer outcomes in people with ovarian and breast cancer, and in those with acute myeloid leukemia.

Results of a previous Phase 1 trial (NCT03401528) in healthy volunteers showed that AVB-500 was safe and well-tolerated, and that it reduced the amount of GAS6 in the blood in a dose-dependent manner.

The therapy — which has the potential to work alone or in combination with standard of care — received fast track designation from the U.S. Food and Drug Administration for chemotherapy-resistant ovarian cancer in 2018.

The ongoing  Phase 1b/2 trial (NCT03639246) is evaluating the safety and efficacy of AVB-500 in combination with standard chemotherapy in women with platinum-resistant ovarian cancer. It started dosing patients at the beginning of the year and is still recruiting at locations across the U.S.

Its open-label Phase 1b portion divides patients into two groups. Each is being given AVB-500 in combination with a chemotherapeutic agent, either pegylated liposomal doxorubicin (PLD) or paclitaxel.

These preliminary efficacy findings, corresponding to the first 12 patients treated, showed that the percentage who responded to either combination is superior to that observed in similar patients given chemotherapy alone in the clinical setting.

Aravive plans to present detailed safety and efficacy trial data at a scientific conference later this year.