# Combating Resistance of Pancreatic Cancer with a First-in-Class Dual Targeted PI3K/EGFR Inhibitor

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2021 · $484,410

## Abstract

Pancreatic cancer is one of the deadliest forms of cancer, with median 5-year survival rates less than 10%.
This disease is recalcitrant to chemotherapeutic approaches and recently approved therapies afford only
modest improvements in survival. KRAS is the most commonly mutated gene in pancreatic tumors with an
incidence rate exceeding 90%. Despite intensive efforts, mutant KRAS (KRASmt) has remained undruggable,
hence kinases acting both upstream and downstream of the RAS signaling cascade continue to be exploited
for the development of novel agents to attenuate signaling through this critical oncogene. MTX-211 is a first-in-
class dual and selective inhibitor of PI3K and EGFR kinase with a promising pharmaceutical profile and ability
to prevent reactivation of ERK signaling than ensues from currently approved MEK inhibitor monotherapies.
Studies are proposed to optimize single agent activity of MTX-211, our clinical candidate (Aim 1), followed by
parallel investigation of two rational combination treatment strategies to further build upon the therapeutic
efficacy of MTX-211. Namely, experimental rationale backed by preliminary data support further investigation
of MTX-211-based combination regimens that incorporate a MEK inhibitor (Aim 2) or an immune checkpoint
inhibitor (Aim 3). Our overall objective is to provide evidence to support clinical development of MTX-211 for
the treatment of KRASmt pancreatic cancer. The proposed studies integrate the use of molecular imaging
reporters and clinically relevant models of pancreatic cancer to conduct mouse trials that will inform future
clinical trial design in a manner which is most likely to impact the management of patients with pancreatic
cancer.

## Key facts

- **NIH application ID:** 10197037
- **Project number:** 5R01CA241764-03
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Judith S Leopold
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $484,410
- **Award type:** 5
- **Project period:** 2019-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10197037

## Citation

> US National Institutes of Health, RePORTER application 10197037, Combating Resistance of Pancreatic Cancer with a First-in-Class Dual Targeted PI3K/EGFR Inhibitor (5R01CA241764-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10197037. Licensed CC0.

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