# Neoadjuvant PD-1 blockade in mismatch repair deficient rectal cancer

> **NIH NIH R21** · SLOAN-KETTERING INST CAN RESEARCH · 2022 · $202,732

## Abstract

ABSTRACT
Rectal cancer is treated with induction chemotherapy followed by chemoradiationand subsequentsurgery. Most
patients who have undergone this sequential treatment approach have significant tumor downstaging , and up to
30% achieve complete clinical and pathologic responses. Approximately 5-10%of all rectal cancers are deficient
in mismatch repair (dMMR) and tumors with this genetic defect respond poorly to standard therapy. Studies in
metastatic patients with dMMR have demonstrated durable response to checkpoint inhibition, with nearly 20%
achieving a complete clinical response with PD-1 blockade. We seek to improve outcomes in dMMR rectal
cancers by treatment with upfront PD-1 blockade with or without standard chemoradiotherapy, with the goal of
increasing the number of complete clinical responses and improving the chances of organ preservation and
reduction in morbidity. Our proposed clinical trial incorporates neoadjuvant PD-1 blockade in patients with dMMR
locally advanced rectal cancer. Utilizing collected biospecimens from patients enrolled in this trial we will use
genomic assessments to determine if the intrinsic features of these dMMR rectal tumors can predict for
resistance or response to PD-1 blockade (Aim 1) and determine if we can predict which patients will achieve
long-term benefit from neoadjuvant PD-1 blockade using circulating tumor DNA (ctDNA) to monitor tumor
response (Aim 2).

## Key facts

- **NIH application ID:** 10335949
- **Project number:** 5R21CA252519-02
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **Principal Investigator:** Andrea Cercek
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $202,732
- **Award type:** 5
- **Project period:** 2021-02-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10335949

## Citation

> US National Institutes of Health, RePORTER application 10335949, Neoadjuvant PD-1 blockade in mismatch repair deficient rectal cancer (5R21CA252519-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10335949. Licensed CC0.

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