DNX-2440 for Resectable Colorectal Liver Metastasis

Sponsor
DNAtrix, Inc. (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04714983
Collaborator
H. Lee Moffitt Cancer Center and Research Institute (Other)
30
1
3
34.5
0.9

Study Details

Study Description

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
30 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase I Safety and Window-of-opportunity Study of Preoperative Intratumoral Injection of OX40-ligand Expressing Oncolytic Adenovirus (DNX-2440) in Patients With Resectable Liver Metastasis
Actual Study Start Date :
Feb 15, 2021
Anticipated Primary Completion Date :
Jul 31, 2022
Anticipated Study Completion Date :
Dec 31, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: Dose-level 1

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

Experimental: Dose-level 2

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

Experimental: Dose-level 3

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

Outcome Measures

Primary Outcome Measures

  1. 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

  1. 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

  2. Viral replication [3 Years]

    Viral replication will be assessed by quantitative measurement of viral protein expression by IHC

  3. 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).

  4. Measure Immune response with ImmunoSEQsec [3 Years]

    Immunotherapeutic responses will be assessed by measuring changes in T-cell receptor (TCR) repertoire - tissue and blood.

  5. Measure Immune response with ELISPOT [3 Years]

    Immunotherapeutic responses will be assessed by measuring T-cell response (ELISPOT - tissue/blood).

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Key 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

Contacts and Locations

Locations

Site City State Country Postal Code
1 H. Lee Moffitt Cancer Center and Research Institute, Inc. Tampa Florida United States 33612

Sponsors and Collaborators

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

Investigators

  • Study Director: Joan Robbins, Ph.d, DNAtrix, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
DNAtrix, Inc.
ClinicalTrials.gov Identifier:
NCT04714983
Other Study ID Numbers:
  • 2440LM-002
First Posted:
Jan 20, 2021
Last Update Posted:
Apr 6, 2022
Last Verified:
Mar 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of Apr 6, 2022