The first part of a Phase 1b/2 trial evaluating the combination of Aravive Biologics’ investigational therapy AVB-S6-500 with standard-of-care therapies in patients with platinum-resistant recurrent ovarian cancer has begun treating patients.
Patient enrollment is ongoing at several U.S. locations, with additional study sites yet to open.
AVB-S6-500, Aravive’s lead treatment candidate, is intended to bind to a protein called Gas6 with high affinity, blocking activation of the GAS6-AXL signaling pathway by reducing or preventing the interaction of GAS6 with the AXL receptor.
Elevated levels of GAS6 have been linked with metastasis, having a more aggressive cancer, treatment resistance, and poorer survival in people with advanced ovarian and breast cancer, and in people with acute myeloid leukemia.
In a prior Phase 1 trial (NCT03401528) in 43 healthy volunteers, treatment with AVB-S6-500 was safe and well-tolerated, with neither serious adverse events nor dose-limiting adverse events being reported. Patients receiving increasing doses of the treatment exhibited a dose-dependent reduction in circulating free GAS6, also lasting longer with higher doses of the therapy. Also, the affinity of AVB-S6-500 to GAS6 was 100 times higher than that of GAS6 to AXL.
In turn, work in preclinical models of acute myeloid leukemia and other advanced solid tumors showed that preventing the GAS6-AXL binding stopped tumor progression. This inhibition of GAS6-AXL was achieved via AVB-S6-500 or other standalone approaches, as well as through strategies including radiation therapy, immuno-oncology, and chemotherapy.
The open-label Phase 1b safety portion aims to confirm the experimental therapy’s dose found in the Phase 1 trial. The primary goal for this part is safety and pharmacological measurements, with secondary goals including preliminary activity measures. The study will also address the effects of AVB-S6-500 on biomarkers such as circulating free GAS6.
In the Phase 2 portion, researchers will determine whether AVB-S6-500, in combination with standard of care treatments, is better than standard of care at delaying disease progression or death. Researchers will also measure the proportion of patients who respond to treatment, duration of responses, overall survival, and quality of life.
“We are very pleased to initiate this first trial of AVB-S6-500 in patients with ovarian cancer,” Gail McIntyre, PhD, Aravive’s senior vice president of research and development, said in a press release. McIntyre said Aravive anticipates that measuring free GAS6 in the blood “will be highly useful as a biomarker of drug activity in this new trial. A reduction in this biomarker has correlated to anti-tumor activity in preclinical studies.”
In August 2018, the U.S. Food and Drug Administration granted fast track designation to AVB-S6-500 to accelerate its development as a potential therapy for platinum-resistant ovarian cancer.