DNX-2440 for Resectable Colorectal Liver Metastasis

DNAtrix

Status and phase: Suspended; Phase 1

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

Treatments: Biological: DNX-2440

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT04714983

2440LM-002

Details and patient eligibility

About

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.

Enrollment: 30 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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30 participants in 3 patient groups

Dose-level 1

Experimental group

Description:

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.

Treatment:

Biological: DNX-2440

Dose-level 2

Experimental group

Description:

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.

Treatment:

Biological: DNX-2440

Dose-level 3

Experimental group

Description:

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.

Treatment:

Biological: DNX-2440