Aravive is recruiting participants for a Phase 1/2 clinical trial assessing a combination of its experimental treatment AVB-500 plus the immune checkpoint inhibitor Imfinzi (durvalumab) in women with platinum-resistant epithelial ovarian cancer.
The trial (NCT04019288) is ongoing at the MD Anderson Cancer Center, in Texas, and is expected to include 36 participants with high grade epithelial ovarian, peritoneal, or fallopian tube cancer who have no standard-of-care treatment options available.
AVB-500 is a fusion protein that binds with high affinity to the GAS6 protein, and works as a decoy that significantly reduces or prevents GAS6’s ability to bind and stimulate the AXL receptor pathway — which plays a key 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.
“We believe there is a strong mechanistic and clinical rationale for exploring the potential of AVB-500 in combination with a checkpoint inhibitor in the treatment of ovarian cancer,” Gail McIntyre, PhD, chief scientific officer of Aravive, said in a press release.
After showing the therapy’s safety and tolerability in healthy people, Aravive initiated a Phase 1/2 trial (NCT03639246) evaluating a combination of AVB-500 plus standard chemotherapy — pegylated liposomal doxorubicin or paclitaxel — in women with platinum-resistant ovarian cancer.
Data from the first 12 patients suggest that responses to either combination are superior to those observed in similar patients given chemotherapy alone in the clinical setting.
In addition to turning off AXL signaling in cancer cells, leading to cancer cell death, AVB-500 also stimulates innate immune responses against solid tumors, suggesting it could work in combination with immune checkpoint inhibitors, such as Imfinzi.
Imfinzi is a human monoclonal antibody that binds to the PD-L1 protein on cancer cells and prevents its interaction with proteins found on the surface of immune cells (known as PD-1 and CD80). This prevents tumours from evading being targeted and killed by the immune cells.
The ongoing Phase 1/2 trial will evaluate the combination in two parts.
The Phase 1b, dose-escalation part is designed to establish the optimal dose for further testing. In this part, patients will receive ascending doses of AVB-500 on days 1 and 15 of each four-week cycle, along with a fixed dose of Imfinzi on day one of every cycle. Both treatment are given as into-the-vein injections.
In Phase 2, participants will be randomized to receive either AVB-500 or Imfinzi for six weeks, followed by subsequent four-week cycles of the combination therapy. Treatment will be given until disease progression or unacceptable toxicity occurs.
After completing treatment, patients will be followed up every six weeks for at least three months. The primary goal of this part is to assess safety in both the single treatment phase and the combination therapy phase.
“There is a significant need for effective treatments that don’t add to the treatment burden for women with ovarian cancer,” said Laura Bonifacio, PhD, vice president of clinical operations at Aravive.
AVB-500 has been granted fast track status by the U.S. Food and Drug Administration for the treatment of platinum-resistant ovarian cancer. The designation is to help expedite the clinical development of investigational therapies for serious conditions.