# Phase 1 Study of DNX-2440 for Resectable Colorectal Liver Metastasis - IND 018569

> **NIH NIH R44** · DNATRIX, INC. · 2022 · $852,568

## Abstract

PROJECT SUMMARY/ABSTRACT
Approximately half of all patients diagnosed with colorectal cancer develop liver metastases (stage 4 disease)
and have a poor prognosis. Surgical resection remains the standard of care for 10-30% of patients with
colorectal liver metastasis, but the recurrence rate for these patients is high (60-80%). Oncolytic virus
immunotherapy represents a novel therapeutic approach for liver metastasis, combining cell killing by oncolysis
and immune-mediated effects that are crucial for response durability. DNX-2440 is a tumor-selective,
conditionally-replicative oncolytic adenovirus encoding human OX40 ligand (OX40L), developed to treat
cancer. DNX-2440 combines in a single agent the oncolytic activity and anti-tumor immune activity of the
predicate adenovirus, DNX-2401 (tasadenoturev) which has completed Phase 2 testing in recurrent
glioblastoma, with additional immune modulation mediated by OX40 pathway engagement. The OX40L genetic
modification in DNX-2440 enhances immune activation within the tumors, as engagement of the OX40
receptor by OX40L enhances memory T-cell survival and suppresses the differentiation and activity of
regulatory T-cells. Preclinical studies demonstrate that DNX-2440 leads to high expression levels of OX40L,
tumor-specific anti-tumor immune memory, and effective cell killing in both injected and non-injected tumors.
In this application, a Phase 1 open-label, window-of-opportunity study is proposed to assess the clinical safety
and anti-tumor immune response to neoadjuvant DNX-2440 in patients with resectable liver metastasis. The
study intervention includes two sequential intratumoral injections of DNX-2440, two weeks apart, to a single
lesion of liver metastasis (target lesion) in patients presenting with two or more lesions of liver metastasis and
scheduled to have surgery for resection of all lesions. This study will evaluate the safety and maximum
tolerated dose of intratumoral administration of DNX-2440 and will provide extensive information about the
biological and immunotherapeutic effects of DNX-2440 in the studied patient population. Correlative analyses
will be performed on collected pre-treatment tumor biopsies from the target lesion and post-treatment tissue
(injected lesion, non-injected lesions, normal tissue) collected during the surgical resection.

## Key facts

- **NIH application ID:** 10475394
- **Project number:** 1R44CA268421-01A1
- **Recipient organization:** DNATRIX, INC.
- **Principal Investigator:** Joan Marie Robbins
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $852,568
- **Award type:** 1
- **Project period:** 2022-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10475394

## Citation

> US National Institutes of Health, RePORTER application 10475394, Phase 1 Study of DNX-2440 for Resectable Colorectal Liver Metastasis - IND 018569 (1R44CA268421-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10475394. Licensed CC0.

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