# Project 2: Inhibiting AXL to Improve Treatment Response in Endometrial Cancer

> **NIH NIH P50** · WASHINGTON UNIVERSITY · 2024 · $413,218

## Abstract

PROJECT SUMMARY
The prognosis for the aggressive histologies in uterine cancer patients is low. This is likely due to lack of
identification of pathways specific to uterine serous cancer or high-grade endometrioid tumors specifically. Our
data suggest that the AXL pathway is highly expressed in uterine serous (USC) and grade 3 endometrioid
endometrial cancer (G3 EEC) is associated with worse survival. We have recently shown that high-affinity,
highly-selective inhibitor of AXL, AVB-500 (now known as batiraxcept), can improve response to paclitaxel in
USC and G3 EEC. Additionally, there is developing data that AXL expression is correlated with the highly
glycolytic phenotype, and this correlation with glycolysis may allow us to determine which tumors can respond
better to AXL inhibition. Furthermore, published data supports that AXL regulates VEGF-A, and our preclinical
data supports that inhibition of AXL can improve response to the anti-angiogenic agent, bevacizumab. Our
central hypothesis is that inhibiting GAS6/AXL with AVB-500 will improve response to standard of care
treatment. We will expand to test this hypothesis in three specific aims.
Aim 1: Determine the safety and tolerability of combining batiraxcept with standard-of-care paclitaxel in
patients with recurrent, aggressive endometrial cancer histologies (USC and G3 EEC).
Exploratory Aim 2: Identify tissue and blood markers that correlate with response to treatment.
Aim 3: Determine the mechanisms by which batiraxcept improves response to the standard-of-care anti-
angiogenic bevacizumab.
Impact: The clinical trial data from Aim 1 will form the foundation of a future Phase II trial of batiraxcept plus
paclitaxel in USC and G3 EEC patients. The data from Exploratory Aim 2 may allow us to develop a metabolic
biomarker that can predict sensitivity to this drug combination and/or provide insight into the metabolic
processes involved in tumors that do not respond to this drug combination. The data from Aim 3 will provide
key mechanistic data to support a future clinical trial combining batiraxcept with bevacizumab. In the long term,
this work will allow us to optimize and personalize treatment for patients with aggressive uterine cancer types.
Our team is well-positioned to test our central hypothesis in clinical and experimental studies.

## Key facts

- **NIH application ID:** 10912618
- **Project number:** 5P50CA265793-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** David G Mutch
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $413,218
- **Award type:** 5
- **Project period:** 2023-08-23 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10912618

## Citation

> US National Institutes of Health, RePORTER application 10912618, Project 2: Inhibiting AXL to Improve Treatment Response in Endometrial Cancer (5P50CA265793-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10912618. Licensed CC0.

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