Aravive announced the independent Data Monitoring Committee (DMC) has reviewed the open-label data following the first 28-day treatment cycle for the three patients in each of the two 15 mg/kg dosing cohorts of the Phase 1b portion of the Phase 1b/Phase 2 clinical trial of AVB-500 in patients with platinum-resistant recurrent ovarian cancer (PROC) and unanimously recommended the study continue as planned with enrollment of patients into the 20mg/kg dose cohorts. The DMC did not identify any safety concerns with AVB-500.

On November 20, 2019, Aravive reported data from the first 31 patients treated at the 10mg/kg dose supporting a relationship between AVB-500 blood levels and anti-tumor response, confirming the company’s strategy to investigate higher doses of AVB-500, specifically 15 and 20 mg/kg every two weeks.

"We are very pleased to receive this positive recommendation by the DMC and that AVB-500 continues to be well-tolerated as predicted from toxicology studies," said Laura Bonifacio, Pharm.D., Ph.D., vice president of clinical operations of Aravive. "Our data modeling has predicted a dose of 20 mg/kg should allow at least 90% of the patients to achieve the desired high drug exposure levels of AVB-500 that correlated to better outcomes in our clinical studies to date."

The company anticipates reporting safety and pharmacokinetic data from this Phase 1b trial in mid-2020 with plans to present preliminary efficacy in 2H 2020. The company plans to initiate a randomized Phase 2/3 study in PROC by end of 2020.

About Platinum-resistant, Recurrent Epithelial Ovarian Cancer (PROC) In the United States, ovarian cancer ranks fifth in cancer deaths among women, accounting for more deaths than any other cancer of the female reproductive system. It is estimated that in 2020 in the United States, more than 21,000 women will develop ovarian cancer and there will be approximately 13,940 attributed deaths.

The open label Phase 1b safety lead-in portion of the efficacy and safety study of AVB-500 in patients with platinum-resistant recurrent ovarian cancer is enrolling patients into two cohorts, one investigating a combination of AVB-500 with pegylated liposomal doxorubicin, and the other, a combination of AVB-500 with paclitaxel. The primary objectives are to assess safety and tolerability of the combinations and to identify the dose for the Phase 2 portion of the study. The clinical trial will also explore secondary endpoints including preliminary activity measures and effects on biomarkers (GAS6-AXL) in serum and tumor tissues.

AVB-500 is a therapeutic recombinant fusion protein that has been shown to neutralize GAS6 activity by binding to GAS6 with very high affinity. In doing so, AVB-500 selectively inhibits the GAS6-AXL signaling pathway. In preclinical studies, GAS6-AXL inhibition has shown anti-tumor activity, both as a single agent and in combination with a variety of anticancer therapies including radiation therapy, immuno-oncology agents and chemotherapeutic drugs that affect DNA replication and repair. Increased expression of AXL and GAS6 in tumors is correlated to poor prognosis and survival, and has been implicated in therapeutic resistance to conventional chemotherapeutics and targeted therapies.

Aravive reported positive data from the first 31 patients enrolled in the Phase 1b portion of a Phase 1b/2 clinical trial of AVB-500 in platinum-resistant recurrent ovarian cancer. AVB-500 continues to be well tolerated with no dose limiting toxicities. An investigator-sponsored Phase 1 study of AVB-500, in combination with durvalumab in patients with platinum-resistant recurrent epithelial ovarian cancer, is also ongoing. Based on AVB-500’s safety profile and specifically targeted mechanism of action, this drug candidate has the potential to be used both in combination with existing therapies, as well as a maintenance drug. The U.S. Food and Drug Administration (FDA) granted Fast Track Designation to AVB-500 in platinum-resistant recurrent ovarian cancer.

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