# Individualized monitoring of treatment response and resistance in patients with metastatic melanoma

> **NIH NIH R01** · TRANSLATIONAL GENOMICS RESEARCH INST · 2020 · $415,333

## Abstract

PROJECT SUMMARY/ABSTRACT:
Metastatic melanoma is a lethal disease with a dismal 20% five-year survival. Immunotherapy and molecularly
targeted treatments improve survival but responses vary across patients and benefits are often temporary due
to disease progression. There are no established circulating biomarkers to monitor treatment response.
Molecular heterogeneity between metastatic tumors within a patient (intra-tumor heterogeneity) and treatment-
driven clonal evolution complicate choice and scheduling of treatments and limit duration of response.
Circulating levels of cancer mutations in cell-free plasma DNA (ctDNA) strongly correlate with treatment
response and disease progression in breast and colorectal cancer. The goal of this project is to assess the
utility of a ctDNA-based blood test for treatment monitoring and as a minimally-invasive alternative to tumor re-
biopsies for tumor genotyping in patients with metastatic melanoma. This goal will be pursued through analysis
of serial plasma, tumor and germline samples from patients with metastatic melanoma from three cohorts: 1) a
completed clinical trial of anti-PD1 immunotherapy; 2) prospective collection from the Stand Up To Cancer
Genomically Enabled Medicine for Melanoma trial; and 3) a prospective observational study of patients at
Mayo Clinic Arizona, treating with standard of care immunotherapy and molecularly targeted drugs.
The specific aims of this proposal are 1) to assess clinical validating of ctDNA as a biomarker for monitoring
treatment response; 2) to evaluate ctDNA sequencing as an alternative to tumor biopsies to guide treatment
selection and 3) to identify genomic drivers of acquired resistance to immunotherapy. For Aim 1, patient-
specific mutations will be identified using tumor exome sequencing, followed by targeted digital sequencing to
quantify ctDNA. Changes in ctDNA levels during treatment will be compared with response and progression on
imaging to assess clinical validity. For Aim 2, concordance of plasma and tumor samples will be assessed
using exome sequencing of pre-treatment plasma DNA and comparison with tumor exome sequencing. For
Aim 3, new genomic alterations arising at disease progression on immunotherapy will be identified using
exome sequencing of post-treatment plasma DNA. Genomic drivers of acquired resistance to anti-PD1
inhibitors will be identified by evaluating molecular pathways recurrently altered at disease progression across
the cohort.
At completion of this project, it is anticipated that the extent to which ctDNA analysis is useful in melanoma for
tumor monitoring, as an alternative to (and potential improvement) over tumor re-biopsies for patient selection
and as an approach for investigating acquired resistance to immunotherapy, will be established.

## Key facts

- **NIH application ID:** 9983765
- **Project number:** 5R01CA223481-03
- **Recipient organization:** TRANSLATIONAL GENOMICS RESEARCH INST
- **Principal Investigator:** Muhammed Murtaza
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $415,333
- **Award type:** 5
- **Project period:** 2018-08-15 → 2020-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9983765

## Citation

> US National Institutes of Health, RePORTER application 9983765, Individualized monitoring of treatment response and resistance in patients with metastatic melanoma (5R01CA223481-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9983765. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*