# Proteogenomic studies to understand mechanisms and drivers of resistance to immunotherapies

> **NIH NIH U01** · FRED HUTCHINSON CANCER CENTER · 2024 · $1,122,409

## Abstract

Project Summary/Abstract
Melanoma is the deadliest form of skin cancer. Its incidence is on the rise with 106,000 new cases expected in
the U.S. in 2021. Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of early and advanced
melanoma, with concurrent anti-CTLA-4 and anti-PD-1 monoclonal antibodies demonstrating a response in
~50% of patients, including highly durable responses. Unfortunately, there are no adequate biomarkers to predict
response to single agent or combination ICI, and dual checkpoint blockade is associated with significant grade
3/4 immune-related adverse events (irAEs) in ~55% of patients. The goals of our PTRC are designed to address
two unmet clinical needs: (i) improve our understanding of mechanisms of resistance to ICIs to design more
effective immunotherapies and combinations, and (ii) identify potential biomarkers to select patients
appropriately for single agent vs combination immunotherapies and to predict and monitor irAEs. In our
Preclinical Arm, we will perform integrated proteogenomic analysis of clinically annotated, pre-treatment biopsies
from melanoma patients who received ICI. The data will be analyzed in the context of clinical annotations to
refine an existing signature of melanoma ICI response identified by our team and to further elucidate mechanisms
of ICI response/resistance and signatures associated with irAEs. In our Clinical Arm, we will analyze clinical trial
biospecimens using MRM-based assays to confirm & extend findings generated in the Preclinical Arm.

## Key facts

- **NIH application ID:** 10862595
- **Project number:** 5U01CA271407-03
- **Recipient organization:** FRED HUTCHINSON CANCER CENTER
- **Principal Investigator:** Diwakar Davar
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,122,409
- **Award type:** 5
- **Project period:** 2022-06-16 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10862595

## Citation

> US National Institutes of Health, RePORTER application 10862595, Proteogenomic studies to understand mechanisms and drivers of resistance to immunotherapies (5U01CA271407-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10862595. Licensed CC0.

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