FDA Grants Fast Track Designation to Batiraxcept for Patients With ccRCC


Following positive new data from a phase 1/2 study examining batiraxcept in patients with clear cell renal cell carcinoma, the agent has been granted fast track designation by the FDA.

The FDA has granted fast track designation to batiraxcept (AVB-S6-500) for the treatment of patients with advanced or metastatic clear cell renal cell carcinoma (ccRCC) who have progressed after 1-2 previous lines of systemic therapy, including immuno-oncology (IO)-based and vascular endothelial growth factor tyrosine kinase inhibitor (VEGF-TKI)-based therapies, according to Aravive, Inc.1

The basis of this fast track designation comes from new data from a phase 1/2 study (NCT04300140) where 26 patients with ccRCC who have been previously treated were administered batiraxcept in the phase 1b portion at doses of 15 mg/kg (n = 16) and 20 mg/kg (n = 10), plus cabozantinib (Cabometyx) 60 mg daily.

Findings revealed there to be no dose limiting toxicities observed in patients who were administered either dose. Among 14 of the 26 patients, the objective response rate (ORR) was 57% and the median progression-free survival (PFS) was 11.4 months.

“The majority of patients with kidney cancer develop resistance to frontline treatment and there is a clinical need for novel agents to improve upon treatment options in the refractory setting,” said Kathryn Beckermann, MD, PhD, assistant professor, division of hematology and oncology, Vanderbilt University Medical Center, and lead investigator for the trial, in the press release. “Response rates to single agent targeted kinase inhibitors are approximately 30% with a PFS of approximately 7 months. The early data seen with batiraxcept except biomarker development, response rate, and progression-free survival are promising.”

In this phase 1b/2 study, investigators are evaluating the safety and efficacy of batiraxcept combined with cabozantinib, batiraxcept in combination with cabozantinib and nivolumab (Opdivo) and batiraxcept alone in patients with advanced or metastatic ccRCC.2

There are 2 portions of the trial. The open-label phase 1b part includes patients with advanced ccRCC who had progressed on or after at least 1 prior line of treatment. They will be administered batiraxcept plus cabozantinib at 1 of 2 dose levels. Then in the phase 2 open-label, 3-part portion of the study, the efficacy and tolerability of batiraxcept combined with cabozantinib, batiraxcept and cabozantinib and nivolumab, and batiraxcept alone will be evaluated.

Enrollment is open to patients aged 18 years and older with histologically confirmed ccRCC who have progressed on/after at least 1 front-line of treatment, have no prior systemic treatment and are not amenable to curative intent therapy.

Additional requirements include having radiologic imaging with a CT scan or MRI within 28 days of enrollment, a life expectancy of >12 weeks, at least 1 measurable lesion according to RECIST 1.1, an ECOG performance status of 0-1, adequate bone marrow, liver, and kidney function, and at least 28 days between the end of a previous major surgery or anticancer therapy or 14 days from last radiation therapy and administration of batiraxcept.

Primary end points of the study include incidence of adverse events, recommended phase 2 dose of the study, the anti-tumor activity of batiraxcept plus cabozantinib, batiraxcept plus nivolumab, and batiraxcept alone, including ORR, duration of response, clinical benefit rate, PFS, and overall survival. Secondary end points consist of pharmacokinetics, anti-drug antibody titers, anti-tumor activity, safety, and tolerability.

Recent data announced comes from the phase 1b portion of the trial which examined patients with advanced or metastatic ccRCC who progressed after 1 or 2 previous lines of immuno-oncology (IO)- and VEGF-TKI-based therapies. These new findings showed there to be an ORR of 57% and a median PFS of 11.4 months among those in the study.

These data show the potential batiraxcept has in increasing the clinical activity of cabozantinib in patients with metastatic ccRCC who have progressed following IO- and VEGF-TKI-based therapies.

“A review of the literature suggests that the clinical activity of cabozantinib is lower in those patients who have progressed following a VEGF-TKI-based therapy compared to patients who have progressed on IO or IO/IO therapy. Since preclinical data published by Xiao in 2019 observed that batiraxcept may restore TKI sensitivity, it makes sense that the combination of batiraxcept and cabozantinib may exhibit its greatest impact in those patients who have failed prior VEGF-TKI therapies,” said Gail McIntyre, PhD, DABT, chief executive officer of Aravive, in the press release. “Understanding the P1b ccRCC data has allowed us to identify the most appropriate patient population in which to evaluate batiraxcept in combination with cabozantinib and potentially the quickest path to approval in this population with an unmet medical need.”

Aravive announces fast track designation of batiraxcept for treatment of ccRCC. News Release. Aravive Inc. November 29, 2022. Accessed November 30, 2022. https://bit.ly/3XJlL9q
Safety and efficacy study of AVB-S6-500 (Batiraxcept) in patients with advanced or metastatic clear cell renal cell carcinoma. ClinicalTrials.gov. Updated August 9, 2022. Accessed November 30, 2022. https://clinicaltrials.gov/ct2/show/NCT04300140
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