# Repositioning Immunotherapy in Veterans with Lung Cancer

> **NIH VA I01** · VETERANS HEALTH ADMINISTRATION · 2024 · —

## Abstract

PROJECT SUMMARY
Lung cancer is the deadliest cancer in American war Veterans. Due to limited uptake in lung cancer screening,
one third of patients present locally advanced (Stage III) non-small cell lung cancer (NSCLC) at diagnosis, and
the overwhelming majority have unresectable disease. The addition of adjuvant immune checkpoint blockade
(ICB) to concurrent chemoradiotherapy (CRT) has resulted in significant improvements in overall survival at five
years for unresectable Stage III NSCLC. Unfortunately, up to a quarter of Veterans with Stage III lung cancer
are unable to tolerate this trimodality therapy. An equal proportion of Veterans discontinue therapy secondary to
treatment progression, highlighting the need for both more effective and better tolerated treatment strategies. In
resectable NSCLC, neoadjuvant immunotherapy can induce major pathologic responses (MPR) in up to half of
patients. Neoadjuvant therapy is better tolerated in many solid malignancies including locally advanced rectal
cancer. Moreover, neoadjuvant immunotherapy more than halves the recurrence rate as compared to adjuvant
immunotherapy in locally advanced melanoma. We hypothesize that 1.) neoadjuvant chemoimmunotherapy will
improve the progression-free survival of patients with unresectable Stage III NSCLC, 2.) PET-adaptive
radiotherapy after neoadjuvant chemoimmunotherapy will reduce radiation field sizes and will enhance the
treatment tolerance and outcomes in Veterans with unresectable NSCLC. We will test this hypothesis in two
aims: Specific Aim 1: Conduct a multi-site single arm open label Phase II clinical trial to assess if neoadjuvant
chemoimmunotherapy followed by adaptive radiotherapy is effective in Veterans with unresectable Stage III
NSCLC. Up to thirty Veterans with unresectable Stage III NSCLC with ≥ 1% PD-L1 expression will be enrolled
across seven VAs. Three cycles of neoadjuvant chemoimmunotherapy will be given followed by PET-adaptive
radiotherapy and adjuvant nivolumab. The primary endpoint of the trial will be the median progression-free
survival. Secondary endpoints will include treatment tolerance, completion of planned courses of therapy, best
overall response rate, and overall survival. Matched controls will be drawn from a contemporaneous cohort of
Veterans with unresectable Stage III NSCLC enrolled on an observational prospective study. We anticipate that
completion of this work will identify that neoadjuvant chemoimmunotherapy will improve patient outcomes and
treatment tolerance. Specific Aim 2: Examine whether baseline and on-treatment factors are indicative of anti-
tumor immunity and clinical benefit from chemoimmunotherapy in Veterans with unresectable Stage III NSCLC.
Preliminary data suggests that tissue immunophenotype may be predictive of benefit from ICI in the metastatic
setting. We will perform correlative exploratory analyses of tissue samples of patients enrolled in this trial to
extend these findings to Stage III NSCLC. In Aim ...

## Key facts

- **NIH application ID:** 10916686
- **Project number:** 1I01CX002665-01A2
- **Recipient organization:** VETERANS HEALTH ADMINISTRATION
- **Principal Investigator:** NITHYA RAMNATH
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2024-07-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10916686

## Citation

> US National Institutes of Health, RePORTER application 10916686, Repositioning Immunotherapy in Veterans with Lung Cancer (1I01CX002665-01A2). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10916686. Licensed CC0.

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