Combination therapy with investigational agent batiraxcept plus cabozantinib (Cabometyx) was safe and showed promising clinical activity in patients with clear cell renal cell carcinoma (ccRCC), according to findings from a phase 1b/2 trial presented during the 36th Annual Society for Immunotherapy of Cancer (SITC) Meeting.1,2
In this preliminary open-label trial, 44% (n = 7) of 16 evaluable patients achieved a partial response across the 2 batiraxcept dose levels explored in the trial (15 mg and 20 mg). The other 9 (56%) patients had a best overall response of stable disease. There were no reports of progressive disease.
“We are encouraged by batiraxcept's early profile in patients with clear cell renal cell carcinoma,” Gail McIntyre, PhD, CEO of Aravive, the developer of the GAS6-AXL pathway inhibitor batiraxcept, stated in a recent news release.2 “The current response rate of batiraxcept in combination with cabozantinib is encouraging. Cabozantinib alone produces response rates between 17%-28% in a similar population. In heavily pretreated patients, batiraxcept demonstrates clinical activity across the 15 mg/kg and 20 mg/kg doses with a tolerable safety profile.”
Additional data showed that among patients with a minimum of 16 weeks’ follow-up (at least 2 post-baseline radiological exams), 5 (71%) out of 7 patients had confirmed partial responses, and the remaining patients (2/7; 29%) had confirmed stable disease.
Overall, 14 (88%) out of 16 patients had a decrease in tumor size from baseline. Four patients had 1 or more target lesions disappear completely. Of those patients, 3 were treated with 15 mg/kg of batiraxcept plus cabozantinib and 1 was treated with 20 mg/kg of batiraxcept plus cabozantinib. Two other patients were observed to have a 76% decrease in target lesions from baseline. Of those patients, 1 each received the 15 mg/kg and 20 mg/kg doses of batiraxcept, respectively.
The safety data revealed that there were no reports of serious adverse events (grade 4/5) related to batiraxcept. Three patients experienced grade 3 adverse events, including hypertension, thrombocytopenia, bowel obstruction, abdominal pain, and vomiting; however, the authors noted that these are all common events associated with the use of cabozantinib.
“The initial phase 1b data of batiraxcept in combination with cabozantinib are impressive and point toward the role of dual AXL and VEGF inhibition in the treatment of clear cell renal cell carcinoma,” added Eric Jonasch, MD, professor of Medicine, The University of Texas MD Anderson Cancer Center. “These early signs of clinical activity coupled with a manageable safety profile introduce a potential new therapeutic approach for patients with advanced kidney cancer.”
1. Beckermann K, Vogelzang NJ, Shifeng M, et al. A Phase 1b/2 randomized study of AVB-S6-500 in combination with cabozantinib versus cabozantinib alone in patients with advanced clear cell renal cell carcinoma who have received front-line treatment. Paper presented at: 36th Annual Society for Immunotherapy of Cancer Meeting; November 10-14, 2021; Washington, DC. Abstract 424.
2. Aravive announces positive preliminary data from phase 1b trial evaluating batiraxcept (AVB-500) in combination with cabozantinib for treatment of clear ell renal cell carcinoma. Aravive. Aravive. November 12, 2021. Accesses November 18, 2021. https://ir.aravive.com/news-releases/news-release-details/aravive-announces-positive-preliminary-data-phase-1b-trial-0