HRX215, A First Generation MKK4 Inhibitor Drug, for the Treatment of Patients With Colorectal Liver Metastasis After Undergoing a Portal Vein Embolization

Summary

This phase IIb trial tests the effect of HRX215 in treating patients with colorectal cancer that has spread from where it first started to the liver (liver metastasis) after undergoing a portal vein embolization (PVE). Currently, surgery to remove the tumor (hepatectomy) remains the only potential treatment for cure. However, less than 30% of patients are considered resectable (can be removed by surgery) at the time of diagnosis. The risk of liver failure and other complications rise with larger areas liver that is removed during surgery. Therefore, the potential for surgery is determined by the amount of liver that will remain after resection. PVE is a standard strategy to increase the potential for resection. A PVE is a procedure that blocks the portal vein (a blood vessel that carries blood to the liver) to prevent flow of blood to the tumor. HRX215 targets and binds to MKK4, a protein found on liver cells plays a part in cellular growth and prevents liver repair and regrowth of cells and tissue. Blocking the activity of MKK4 may help prevent liver failure, protect liver cells and improve liver mass. Giving HRX215 after a PVE may help improve the rate of liver regrowth and increase the likelihood of hepatectomy in patients with colorectal liver metastasis.

Conditions

• Metastatic Colorectal Carcinoma
• Metastatic Malignant Neoplasm in the Liver
• Resectable Colorectal Carcinoma
• Stage IV Colorectal Cancer AJCC v8

Interventions

PROCEDURE

Biopsy Procedure

Undergo tissue biopsy

PROCEDURE

Biospecimen Collection

Undergo blood sample collection

PROCEDURE

Computed Tomography

Undergo CT and CT-PET

DRUG

Darizmetinib

Given PO

DRUG

Embolization Therapy

Undergo PVE

PROCEDURE

Hepatectomy

Undergo hepatectomy

PROCEDURE

Magnetic Resonance Imaging

Undergo MRI

DRUG

Placebo Administration

Given PO

PROCEDURE

Positron Emission Tomography

Undergo CT-PET

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

  collaborator NIH

• Mayo Clinic

  lead OTHER

Principal Investigators

• Scott L. Nyberg, MD, PhD · Mayo Clinic in Rochester

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

90 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-09-01

Primary Completion

2028-08-01

Completion

2028-08-01

FDA Drug

Yes

Countries

• United States

Study Locations