DNX-2440 for Resectable Colorectal Liver Metastasis

NCT04714983 | Suspended Phase 1 FDA Drug

• 1 other identifier: 2440LM-002
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Liver Metastases; Liver Metastasis Colon Cancer; Colorectal Cancer; Breast Cancer; Gastric Cancer; Periampullary Cancer; Melanoma; Renal Cell Cancer; Sarcoma; Squamous Cell Carcinoma; Gastrointestinal Stromal Tumors

Outcome Measures

Primary Outcomes (1)

• 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).

  1.5 Years

Secondary Outcomes (5)

• Efficacy of DNX-2440 assessed by Tumor Regression Grade (TRG) score

  3 Years

• Viral replication

  3 Years

• Measure Immune response with cell response panels

  3 Years

• Measure Immune response with ImmunoSEQsec

  3 Years

• Measure Immune response with ELISPOT

  3 Years

Study Arms (3)

Dose-level 1

EXPERIMENTAL

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.

Biological: DNX-2440

Dose-level 2

EXPERIMENTAL

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.

Biological: DNX-2440

Dose-level 3

EXPERIMENTAL

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.

Biological: DNX-2440

Interventions

DNX-2440 BIOLOGICAL

DNX-2440 is a replication competent oncolytic adenovirus expressing human OX40 ligand.

Dose-level 1; Dose-level 2; Dose-level 3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• DNAtrix, Inc.: lead
• H. Lee Moffitt Cancer Center and Research Institute: collaborator

Study Sites (1)

H. Lee Moffitt Cancer Center and Research Institute, Inc.

Tampa, Florida, 33612, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Breast Neoplasms; Stomach Neoplasms; Melanoma; Carcinoma, Renal Cell; Sarcoma; Carcinoma, Squamous Cell; Gastrointestinal Stromal Tumors

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Stomach Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms, Squamous Cell; Neoplasms, Connective Tissue

Study Officials

• Joan Robbins, Ph.d

  DNAtrix, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 9, 2020
• First Posted: January 20, 2021
• Study Start: February 15, 2021
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: April 9, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)