On March 3, 2022 Aravive, Inc. (Nasdaq: ARAV), a late clinical-stage oncology company developing targeted therapeutics to treat metastatic disease, reported positive new data from the Phase 1b portion of the ongoing Phase 1b/2 trial of batiraxcept in clear cell renal cell cancer (ccRCC) and new data from a biomarker high subgroup (Press release, Aravive, MAR 3, 2022, View Source [SID1234609469]).

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As of February 4, 2022, 26 ccRCC patients have been treated with batiraxcept at doses of 15 mg/kg (n=16) and 20 mg/kg (n=10), plus cabozantinib 60 mg daily in previously treated (2L+) patients with ccRCC. Demographics of the evaluated 26 patients are representative of a 2L+ ccRCC population, with all patients having received a prior immunotherapy. Key findings include:

No dose limiting toxicities observed at either the 15 mg/kg or 20 mg/kg batiraxcept dose in combination with cabozantinib
At a median follow-up of 4.9 months on February 4, 2022, 92% of patients remain on study
Best overall response rate (ORR) in the ITT population is 46% (12/26)
In the 15 mg/kg population, best ORR is 56% (9/16)
In the 20 mg/kg population, best ORR is 30% (3/10)
No patient has had progressive disease as their best response
The 6-month progression-free survival (PFS) rate in the ITT population is 79%
Median duration of response (DOR) has not been reached; the 3-month DOR is 100%
Biomarker Data
As previously reported, a key finding from the Company’s Phase 1b trial of batiraxcept in platinum-resistant ovarian cancer is an observable correlation of baseline levels of serum soluble AXL (sAXL)/GAS6 to clinical activity. As such, one of the objectives of the ongoing Phase 1b/2 ccRCC trial is to measure the correlation of baseline sAXL/GAS6 with radiographic response in patients with ccRCC treated with batiraxcept plus cabozantinib. Ratios of sAXL/GAS6 were evaluated retrospectively.

Among the 26 patients treated in the ccRCC trial, 25 were evaluable for baseline sAXL/GAS6. A high ratio optimized a patient’s ability to respond to batiraxcept plus cabozantinib. Key findings from biomarker high patients include:

Best ORR rate in the biomarker high population is 63% (12/19)
In the 15 mg/kg population, best ORR is 75% (9/12)
In the 20 mg/kg population, best ORR is 43% (3/7)
The 6-month PFS rate in the biomarker high population is 77%, with a 6-month PFS rate of 91% in the 15 mg/kg biomarker high group
Median DOR has not been reached in the biomarker high subgroup; the 3-month DOR is 100%
The safety and clinical activity data continue to support 15 mg/kg batiraxcept as an appropriate dose to study in combination with cabozantinib in the Phase 2 ccRCC portion of the study.

"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 Kathryn Beckermann, M.D., Ph.D., Assistant Professor, Division of Hematology and Oncology, Vanderbilt University Medical Center, and lead investigator for the trial. "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 55-65%. Additionally, objective response rates for other preferred National Comprehensive Cancer Network regimens range from 25-37%. 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."

About the Batiraxcept (AVB-500) Phase 1b/2 ccRCC Trial
The Phase 1b trial is evaluating batiraxcept at doses of 15 mg/kg and 20 mg/kg, plus cabozantinib 60 mg daily in previously treated (2L+) patients with ccRCC. Prior treatment with cabozantinib was not allowed. The primary objective is safety; secondary and exploratory objectives include identification of the recommended phase 2 dose (RP2D), objective response rate, and duration of response (DOR). Given baseline levels of serum soluble AXL (sAXL)/GAS6 correlated to clinical activity in the Company’s Phase 1b trial of batiraxcept in platinum-resistant ovarian cancer, one of the objectives of the ccRCC trial is to correlate baseline sAXL/GAS6 with ORR in patients with ccRCC treated with batiraxcept plus cabozantinib.

The open-label Phase 2 portion of the clinical trial initiated earlier this year and is expected to enroll 55 patients across three parts. Part A is expected to enroll approximately 25 patients and investigate batiraxcept 15 mg/kg in combination with cabozantinib in 2L+ ccRCC patients. Part B is expected to enroll approximately 20 patients and evaluate batiraxcept 15 mg/kg in combination with nivolumab and cabozantinib as a potential front-line treatment for ccRCC. Part C is expected to evaluate batiraxcept 15 mg/kg monotherapy in approximately 10 patients with ccRCC who are not eligible for curative intent therapies.