Aravive Announces Phase 3 Trial Design for AVB-500 in Platinum Resistant Ovarian Cancer
Aravive, Inc. recently announced the company has received guidance from the US FDA on a Phase 3 trial design for AVB-500 in platinum-resistant ovarian cancer (PROC). The global, randomized, double-blind, placebo-controlled adaptive trial is designed to evaluate efficacy and tolerability of AVB-500 at a dose of 15 mg/kg in combination with paclitaxel.
“We look forward to advancing AVB-500 into a pivotal Phase 3 trial in platinum resistant ovarian cancer, following the promising results from our Phase 1b trial and productive conversations with the FDA,” said Gail McIntyre, PhD, Chief Executive Officer of Aravive. “With agreement from the FDA that our preclinical and clinical pharmacology programs are now complete, we anticipate that this trial, if successful, could support the submission of a biologics license application to the FDA. We plan to initiate the trial in the first quarter of 2021, with an interim analysis expected a year later.”
The pivotal, adaptive Phase 3 trial is expected to enroll approximately 300-400 patients with high-grade serous ovarian cancer who have received one to four prior lines of therapy. This global trial is planned to be conducted at approximately 100 sites in the US and Europe. The primary endpoint for the trial is progression free survival, and secondary endpoints include overall survival, objective response rate, duration of response, quality of life, clinical benefit rate, and pharmacokinetic and pharmacodynamic profile. Prospectively defined interim analyses will investigate treatment differences in patients who have previously received bevacizumab versus those who have not and will explore the biomarkers identified in the Phase 1b trial in an effort to test the hypotheses generated from the Phase 1b data. Based on the interim analyses, the trial can be adapted to include only those patients who have not previously been treated with bevacizumab and/or whose baseline serum biomarker results meet the identified threshold.
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 preclinical models. In doing so, AVB-500 selectively inhibits the GAS6-AXL signaling pathway, which is upregulated in multiple cancer types including ovarian cancer. In preclinical studies, GAS6-AXL inhibition has shown anti-tumor activity 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 has been correlated with poor prognosis and decreased survival and has been implicated in therapeutic resistance to conventional chemotherapeutics and targeted therapies. AVB-500 is currently being evaluated in clinical trials and has been granted Fast-Track Designation by the US FDA in platinum-resistant recurrent ovarian cancer. Analysis of all safety data to date showed that AVB-500 has been generally well-tolerated with no dose-limiting toxicities or unexpected safety signals.
Aravive, Inc. is a clinical-stage oncology company developing transformative therapeutics designed to halt the progression of life-threatening diseases. Aravive’s lead therapeutic, AVB-500, is an ultra-high affinity decoy protein that targets the GAS6-AXL signaling pathway associated with tumor cell growth. Aravive recently successfully completed a Phase 1b trial of AVB-500 in platinum-resistant ovarian cancer and selected 15 mg/kg as the dose for the Phase 3 trial. While the Phase 1b trial of AVB-500 in platinum-resistant ovarian cancer was a safety trial and not powered to demonstrate efficacy, all 5 patients in the 15 mg/kg cohort experienced clinical benefit, with 1 complete response, 2 partial responses, and 2 stable disease. The company also intends to initiate a Phase 1b/Phase 2 trial of AVB-500 in clear cell renal cell carcinoma later this year. For more information, visit www.aravive.com.
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