DNX-2440 for Resectable Colorectal Liver Metastasis

Phase 1

Suspended

• Conditions: Colorectal Cancer; Squamous Cell Carcinoma; Liver Metastasis Colon Cancer; Melanoma; Sarcoma; Liver Metastases; Gastric Cancer; Periampullary Cancer; Renal Cell Cancer; Gastrointestinal Stromal Tumors
• Interventions: Biological: DNX-2440

• Registration Number: NCT04714983
• Lead Sponsor: DNAtrix, Inc.

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-12-09
• Study First Submitted QC: 2021-01-14
• Study First Posted: 2021-01-20
• Study Start: 2021-02-15
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-05
• Last Update Posted: 2024-04-09
• Primary Completion: 2026-07-31
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: SUSPENDED
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

• Male or female aged ≥ 18 years at time of consent
• Diagnosis of liver metastases from colorectal, breast, gastric, periampullary, melanoma, renal cell cancer, sarcoma, squamous cell carcinoma or gastrointestinal stromal tumor
• Multiple (≥ 2) liver tumors
• Candidate for curative-intent surgery
• Stated willingness to comply with all study procedures and availability for the duration of the study.
• Candidates eligible for targeted therapy, as per standard of care guidelines (and based on mutational status as indicated), must have completed therapy
• Preoperative chemotherapy is allowed

Key

Exclusion Criteria

• Recurrence of liver metastasis
• Diagnosis of neuroendocrine tumor liver metastasis
• Liver metastasis treated with > 12 cycles of systemic chemotherapy
• Condition that requires ongoing systemic immunosuppressive therapy
• Evidence of inadequate organ function based on lab parameters
• Liver transaminases (aspartate aminotransferase [AST] and/or alanine aminotransferase [ALT]) or total bilirubin > 5x the upper limits of normal
• Males or females who refuse to use a double-barrier form of birth control during the study and for up to 6 months after injection with DNX-2440

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Dose-level 1	DNX-2440	The dose-level 1 arm will use a 3+3 design. A single dose of DNX-2440 will be delivered via intra-tumoral injection at Visit 1 and at Visit 3 (2 administrations in total) approximately 14 days apart.
Dose-level 2	DNX-2440	The dose-level 2 arm will use a 3+3 design. A single dose of DNX-2440 will be delivered via intra-tumoral injection at Visit 1 and at Visit 3 (2 administrations in total) approximately 14 days apart.
Dose-level 3	DNX-2440	The dose-level 3 arm will use a 3+3 design. A single dose of DNX-2440 will be delivered via intra-tumoral injection at Visit 1 and at Visit 3 (2 administrations in total) approximately 14 days apart.

Primary Outcome Measures

Name	Time	Method
Maximum tolerated dose (MTD) achieved during dose-escalation phase	1.5 Years	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).

Secondary Outcome Measures

Name	Time	Method
Efficacy of DNX-2440 assessed by Tumor Regression Grade (TRG) score	3 Years	Efficacy in tumor cell killing will be measured using the TRG score (1-5) for the resected specimens
Measure Immune response with ImmunoSEQsec	3 Years	Immunotherapeutic responses will be assessed by measuring changes in T-cell receptor (TCR) repertoire - tissue and blood.
Measure Immune response with cell response panels	3 Years	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).
Viral replication	3 Years	Viral replication will be assessed by quantitative measurement of viral protein expression by IHC
Measure Immune response with ELISPOT	3 Years	Immunotherapeutic responses will be assessed by measuring T-cell response (ELISPOT - tissue/blood).

Trial Locations

Locations (1)

H. Lee Moffitt Cancer Center and Research Institute, Inc.; 🇺🇸 Tampa, Florida, United States