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DNX-2440 for Resectable Colorectal Liver Metastasis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04714983
Recruitment Status : Recruiting
First Posted : January 20, 2021
Last Update Posted : April 6, 2022
Sponsor:
Collaborator:
H. Lee Moffitt Cancer Center and Research Institute
Information provided by (Responsible Party):
DNAtrix, Inc.

Study Description
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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.

Condition or disease Intervention/treatment Phase
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 Biological: DNX-2440 Phase 1

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated 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 : February 15, 2021
Estimated Primary Completion Date : July 31, 2022
Estimated Study Completion Date : December 31, 2023

Resource links provided by the National Library of Medicine


Arms and Interventions
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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
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Primary Outcome Measures :
  1. Maximum tolerated dose (MTD) achieved during dose-escalation phase [ Time Frame: 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 [ Time Frame: 3 Years ]
    Efficacy in tumor cell killing will be measured using the TRG score (1-5) for the resected specimens

  2. Viral replication [ Time Frame: 3 Years ]
    Viral replication will be assessed by quantitative measurement of viral protein expression by IHC

  3. Measure Immune response with cell response panels [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 3 Years ]
    Immunotherapeutic responses will be assessed by measuring T-cell response (ELISPOT - tissue/blood).


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04714983


Contacts
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Contact: Joan Robbins, Ph.d 832-930-2401 2440LM-002study@DNAtrix.com

Locations
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United States, Florida
H. Lee Moffitt Cancer Center and Research Institute, Inc. Recruiting
Tampa, Florida, United States, 33612
Contact: Marjorie Brelsford    813-745-3772    Marjorie.Brelsford@moffitt.org   
Contact: Daniel Anaya, MD    813-745-1813    Daniel.AnayaSaenz@moffitt.org   
Principal Investigator: Daniel Anaya, MD         
Sponsors and Collaborators
DNAtrix, Inc.
H. Lee Moffitt Cancer Center and Research Institute
Investigators
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Study Director: Joan Robbins, Ph.d DNAtrix, Inc.
More Information
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Responsible Party: DNAtrix, Inc.
ClinicalTrials.gov Identifier: NCT04714983    
Other Study ID Numbers: 2440LM-002
First Posted: January 20, 2021    Key Record Dates
Last Update Posted: April 6, 2022
Last Verified: March 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Neoplasm Metastasis
Neoplasms, Second Primary
Liver Neoplasms
Carcinoma, Renal Cell
Gastrointestinal Stromal Tumors
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Neoplasms by Histologic Type
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplastic Processes
 Pathologic Processes
Neoplasms, Connective and Soft Tissue
Liver Diseases
Adenocarcinoma
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 Tissue