The addition of batiraxcept to paclitaxel did not significantly improve progression-free survival compared with paclitaxel alone in a prespecified subset of patients with platinum-resistant ovarian cancer who were not previously exposed to bevacizumab, missing the primary end point of the phase 3 AXLerate-OC trial.
The addition of batiraxcept (AVB-S6-500) to paclitaxel did not significantly improve progression-free survival (PFS) compared with paclitaxel alone in a prespecified subset of patients with platinum-resistant ovarian cancer who were not previously exposed to bevacizumab (Avastin), missing the primary end point of the phase 3 AXLerate-OC trial (NCT04729608).1
Data indicated that in the bevacizumab-naïve subgroup (n = 179), the median PFS with batiraxcept plus paclitaxel was 5.4 months vs 5.4 months with paclitaxel alone. In the overall population, which also included those who previously received bevacizumab, the median PFS was 5.1 months with the combination vs 5.5 months with paclitaxel alone.
Regarding safety, the profile of batiraxcept aligned with what had previously been reported with the agent, and no new signals were observed.
“Although AXLerate-OC did not meet the primary end point, I look forward to working with Aravive to analyze the phase 3 data and determine the most appropriate path to bring batiraxcept to those patients who may benefit most,” Katherine Fuh, MD, PhD, associate professor and director of Basic and Translational Research, and John A. Kerner Chair in Gynecologic Oncology, at the University of California, San Francisco, stated in a press release.
The double-blind, randomized, placebo/paclitaxel-controlled phase 3 trial enrolled patients with histologically confirmed recurrent ovarian, fallopian tube, or peritoneal cancer who had high-grade serous adenocarcinoma histology.2 Patients were required to be at least 18 years of age, have an ECOG performance status of 0 or 1, and have received at least 1 but no more than 4 prior lines of treatment. Patients also needed to have disease that was resistant to platinum therapy and measurable by RECIST v1.1 criteria.
If patients had breast or bone tumors, untreated central nervous system metastases, primary platinum-refractory disease, or evidence of clinically significant third spacing that needed a therapeutic intervention within 28 days before study treatment, they were excluded. Other exclusion criteria included concurrent treatment with anticancer agents or another interventional approach for underlying ovarian cancer.
A total of 366 patients were enrolled to the trial.1 Patients were randomly assigned to receive batiraxcept at 15 mg/kg plus weekly paclitaxel vs placebo plus weekly paclitaxel.3 Patients were stratified based on previous receipt of bevacizumab, and 50% had received the agent before entering the trial.1
The statistical analysis plan comprised a hierarchical approach for PFS assessment in the bevacizumab-naïve subset first, followed by the overall population. In addition to PFS serving as the primary end point of the research, other end points of interest include duration of response, objective response rate (ORR), clinical benefit rate, safety, and quality of life, among others.2
Aravive, Inc. shared plans to continue to examine the complete dataset and identify next steps for the development of this agent.1
“We are conducting additional analyses on the AXLerate-OC phase 3 trial to further evaluate the results of this study and determine the best path forward with our 2 other planned indications in renal cell carcinoma [RCC] and pancreatic cancer,” Gail McIntyre, PhD, DABT, president and chief executive officer of Aravive, Inc., stated in the press release. “We want to thank the patients who participated in this trial, the clinical investigators, and the Aravive team for their hard work, as we continue to pursue our goal of finding innovative cancer treatment for patients in need.”
In November 2022, batiraxcept was awarded fast track designation from the FDA for use as a potential therapeutic option in patients with advanced or metastatic clear cell RCC who have progressed following 1 or 2 lines of systemic treatment that included immuno-oncology (IO)– and VEGF TKI–based therapies, either in combination or sequentially.5
The decision was supported by findings from the phase 1b AVB500-RCC-003 trial (NCT04300140), which showed that the agent was safe and had early evidence of efficacy in pretreated patients with advanced or metastatic disease.6 In the 26 patients who received batiraxcept plus cabozantinib (Cabometyx), the ORR was 57% and the median PFS was 11.4 months. Notably, 14 patients had progressed on IO- and VEGF TKI–based treatments.5