The purpose of this study is to test an experimental oncolytic adenovirus called DNX-2440 in patients with resectable multifocal (≥ 2 lesions) liver metastasis, who are scheduled to have curative-intent liver resection surgery. Up to 18 patients will receive two sequential intra-tumoral injections of DNX-2440 into a metastatic liver tumor prior to surgery for liver resection, to evaluate safety and biological endpoints across 3 dose levels (dose escalation). Upon conclusion of the dose-escalation phase, the selected safe and biologically appropriate dose will be administered using the same schema for an additional 12 patients with colorectal cancer liver metastasis (expansion cohort) using established biologic endpoints.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
30
DNX-2440 is a replication competent oncolytic adenovirus expressing human OX40 ligand.
H. Lee Moffitt Cancer Center and Research Institute, Inc.
Tampa, Florida, United States
Maximum tolerated dose (MTD) achieved during dose-escalation phase
The MTD will be defined as the highest tolerated dose below the dose that results in greater than or equal to one-third of the subjects exposed who experience a dose-limiting toxicity (DLT).
Time frame: 1.5 Years
Efficacy of DNX-2440 assessed by Tumor Regression Grade (TRG) score
Efficacy in tumor cell killing will be measured using the TRG score (1-5) for the resected specimens
Time frame: 3 Years
Viral replication
Viral replication will be assessed by quantitative measurement of viral protein expression by IHC
Time frame: 3 Years
Measure Immune response with cell response panels
Immunotherapeutic responses will be assessed by examining features and measuring changes following the intervention for Immunologic microenvironment (T-cell and Myeloid-cell response panels-tissue).
Time frame: 3 Years
Measure Immune response with ImmunoSEQsec
Immunotherapeutic responses will be assessed by measuring changes in T-cell receptor (TCR) repertoire - tissue and blood.
Time frame: 3 Years
Measure Immune response with ELISPOT
Immunotherapeutic responses will be assessed by measuring T-cell response (ELISPOT - tissue/blood).
Time frame: 3 Years
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