Updated data from the ongoing phase 1b/2 trial of batiraxcept in combination with cabozantinib shows favorable outcomes in patients with clear cell renal cell carcinoma.
New data from the ongoing phase 1b/2 trial of batiraxcept in combination with cabozantinib (Cabometyx) demonstrates favorable outcomes in patients with clear cell renal cell carcinoma (ccRCC), according to Aravive, Inc. (Nasdaq: ARAV).1
Aravive, which is the developer of the GAS6-AXL pathway inhibitor batiraxcept, reported 6-month progression-free survival (PFS) rate and the best overall response rate (ORR) of the intent-to-treat population to be 79% and 46%, respectively.
“We are very encouraged by the best overall response rate and 6-month progression-free survival rate observed in the phase 1b trial of batiraxcept in patients with ccRCC,” said lead investigator Kathryn Beckermann, MD, PhD, assistant professor of hematology and oncology at Vanderbilt University Medical Center in Nashville, Tennessee, in a news release.1 “These data are compelling as the objective response rate in the cabozantinib alone groups of the METEOR and CANTATA studies were 17% and 28%, respectively, and the 6-month progression-free survival rates for cabozantinib from these studies ranged from 55% to 65%.
Additionally, objective response rates for other preferred National Comprehensive Cancer Network regimens range from 25% to 37%.”
The study was developed to evaluate batiraxcept at both 15 mg/kg and 20 mg/kg in addition to cabozantinib at 60 mg daily in patients with ccRCC. These patients had already received immunotherapy.
The primary end point of the trial was safety, with secondary end points consisting of identification of the recommended phase 2 dose, ORR, and duration of response (DOR).
The study enrolled patients aged 18 and older with histologically confirmed advanced or metastatic ccRCC confirmed by imaging. Other requirements included radiologic imaging with a CT scan or MRI within 28 days of enrollment, at least one measurable lesion according to RECIST 1.1, an ECOG performance status of 0-1, and adequate bone marrow, and liver and kidney function.
During the 36th Annual Society for Immunotherapy of Cancer Meeting,2 findings reported showed that across the 2 dose levels, 44% (7/16) of patients achieved a partial response in addition to 56% (9/16) of patients having a best ORR of stable disease. A total of 88% (14/16) of patients showed a decrease in tumor size, and no sign of progressive disease or serious adverse events were reported.2
There have been 26 ccRCC patients treated with the batiraxcept plus cabozantinib combination therapy as of February 4, 2022. No dose limiting toxicities were observed at either the 15 mg/kg or 20 mg/kg batiraxcept dose when combined with cabozantinib. Of those who received 15 mg/kg batiraxcept, the best ORR was 56% (9/16) while that of the group who received 20 mg/kg batiraxcept was 30% (3/10). While the 3-month DOR was 100%, the 6-month DOR has not been reached.
Among the 26 patients, 25 were eligible to be evaluated for baseline serum soluble AXL (sAXL)/GAS6 where a high ratio would indicate an increased likelihood of response to the combination therapy. The 6-month PFS rate and best ORR in the sAXL/GAS6 biomarker-high population was 91% and 63%. For the 15 mg/kg population, best ORR was 75% and 43% for 20 mg/kg population.
“These early data suggest batiraxcept adds to cabozantinib clinical activity and potentially provides a much-needed therapy for this group of patients with refractory clear cell renal cell carcinoma,” said Beckermann.
Both the safety and clinical activity data remain consistent and continue to support 15 mg/kg batiraxcept as an appropriate dose to study when given in combination with cabozantinib in the phase 2 ccRCC part of the study.
The open-label phase 2 portion is expected to enroll 55 patients across 3 parts. Part A will enroll 25 patients treated with 15 mg/kg batiraxcept plus cabozantinib, and part B will enroll 20 patients treated with 15 mg/kg batiraxcept plus cabozantinib and nivolumab. Part C will enroll 10 patients with ccRCC who ineligible for curative intent therapies.