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

NCT07612007 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: MC25041225-010359R01DK140085
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• Future liver remnant size (FLR)

  Will be defined as the percentage of the liver expected to remain after a planned hepatectomy. Will be compared between the two treatment groups \[HRX215 versus (vs) placebo\] utilizing an analysis of covariance (ANCOVA) F-test controlling for age, gender, and FLR at baseline.

  At day 28 post-baseline

Secondary Outcomes (8)

• FLR size

  At day 7 post-baseline

• Incidence of adverse events (AEs)

  Up to 28 days after last dose of study treatment

• Resectability after PVE

  At or after 28 days post-baseline

• Post-hepatectomy liver failure (PHLF)

  Between postoperative days 5 and 7

• Post-operative morbidity

  Up to 360 days post-PVE

Study Arms (2)

Arm I (HRX215, PVE, hepatectomy)

EXPERIMENTAL

Patients undergo scheduled PVE on day 0. Starting 2 hours before undergoing PVE, patients receive HRX215 PO BID (orally twice daily) on days 0-27 in the absence of disease progression or unacceptable toxicity. Starting on or after day 32, patients may undergo scheduled hepatectomy. Patients also undergo blood sample collection, CT, MRI, and CT-PET throughout the study. Additionally, patients may undergo tissue biopsy during scheduled hepatectomy on study.

Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Drug: Darizmetinib; Drug: Embolization Therapy; Procedure: Hepatectomy; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography

Arm II (placebo, PVE, hepatectomy)

PLACEBO COMPARATOR

Patients undergo scheduled PVE on day 0. Starting 2 hours before undergoing PVE, patients receive placebo PO BID (orally twice daily) on days 0-27 in the absence of disease progression or unacceptable toxicity. Starting on or after day 32, patients may undergo scheduled hepatectomy. Patients also undergo blood sample collection, CT, MRI, and CT-PET throughout the study. Additionally, patients may undergo tissue biopsy during scheduled hepatectomy on study.

Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Drug: Embolization Therapy; Procedure: Hepatectomy; Procedure: Magnetic Resonance Imaging; Drug: Placebo Administration; Procedure: Positron Emission Tomography

Interventions

Biopsy Procedure PROCEDURE

Undergo tissue biopsy

Also known as: Biopsy, BIOPSY_TYPE, Bx

Arm I (HRX215, PVE, hepatectomy); Arm II (placebo, PVE, hepatectomy)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

Arm I (HRX215, PVE, hepatectomy); Arm II (placebo, PVE, hepatectomy)

Computed Tomography PROCEDURE

Undergo CT and CT-PET

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Arm I (HRX215, PVE, hepatectomy); Arm II (placebo, PVE, hepatectomy)

Darizmetinib DRUG

Given PO

Also known as: HRX 215, HRX-215, HRX215, LN 3348, LN-3348, LN3348

Arm I (HRX215, PVE, hepatectomy)

Embolization Therapy DRUG

Undergo PVE

Also known as: Embolization, therapy, embolization

Arm I (HRX215, PVE, hepatectomy); Arm II (placebo, PVE, hepatectomy)

Hepatectomy PROCEDURE

Undergo hepatectomy

Also known as: Liver Resection

Arm I (HRX215, PVE, hepatectomy); Arm II (placebo, PVE, hepatectomy)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Arm I (HRX215, PVE, hepatectomy); Arm II (placebo, PVE, hepatectomy)

Placebo Administration DRUG

Given PO

Arm II (placebo, PVE, hepatectomy)

Positron Emission Tomography PROCEDURE

Undergo CT-PET

Also known as: Medical Imaging, Positron Emission Tomography, PET (positron emission tomography), PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, PT

Arm I (HRX215, PVE, hepatectomy); Arm II (placebo, PVE, hepatectomy)

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• REGISTRATION: Adults 18-90 years
• REGISTRATION: Individuals with metachronous colorectal carcinoma liver metastases (CRCLM) after resection of the primary OR synchronous CRCLM with planned simultaneous resection of primary and metastatic disease
• REGISTRATION: Measurable intrahepatic disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) and considered resectable by multidisciplinary tumor board with at least one senior hepatic surgeon
• REGISTRATION: Available CT suitable for volumetric studies on FLR ≤ 21 days
• REGISTRATION: Clinical indication for PVE prior to major hepatectomy as evaluated by at least one senior hepatic surgeon
• REGISTRATION: Estimated life expectancy ≥ 3 months as evaluated and approximated by a senior hepatic surgeon
• REGISTRATION: Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
• REGISTRATION: Platelets ≥ 100,000/mm\^3 (≤ 15 days prior to registration)
• REGISTRATION: Polynuclear neutrophils ≥ 1000/mm\^3 (≤ 15 days prior to registration)
• REGISTRATION: Hemoglobin ≥ 9 g/dL (≤ 15 days prior to registration) (post-transfusion participants can be included)
• REGISTRATION: Creatinine ≤ 1.5 x upper limit of normal (ULN) (≤ 15 days prior to registration)
• REGISTRATION: Bilirubin ≤ ULN (≤ 15 days prior to registration)
• REGISTRATION: Albumin ≥ 3 g/dL (≤ 15 days prior to registration)
• REGISTRATION: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x ULN (≤ 15 days prior to registration)
• REGISTRATION: International normalized ratio ≤ 1.5 (≤ 15 days prior to registration)

You may not qualify if:

• REGISTRATION: Cirrhosis or clinical ascites
• REGISTRATION: Patients with synchronous CRCLM and scheduled staged approach (i.e., resection of metastatic hepatic disease after PVE followed by resection of the colorectal primary in a second operation)
• REGISTRATION: Any liver cancer other than CRLM
• REGISTRATION: Contraindications to imaging or perioperative management:
• Allergy/contraindication to iodine contrast
• Anticoagulation with heparin/antivitamin K (AVK) that cannot be interrupted for 48 hours
• Antiplatelet therapy (e.g., clopidogrel) that cannot be interrupted for 5 days
• REGISTRATION: Inability to discontinue cytochrome P450 (CYP)2D6 inhibitor concomitant medication from start of trial treatment to day 28
• REGISTRATION: Inoperability due to underlying chronic diseases and co-morbidities as assessed by the hepatobiliary surgeon during screening visit
• REGISTRATION: Anticipated need to start adjuvant chemotherapy prior to completion of 28 day treatment period
• REGISTRATION: Positive test at screening for active hepatitis B virus (HBV)/hepatitis C virus (HCV), defined as history of seropositivity for hepatitis B virus (unless immune due to vaccination or resolved natural infection or unless passive immunization due to immunoglobulin therapy), i.e., positive test for anti-hepatitis B core antigen and negative test for anti-hepatitis B surface antibody. Ongoing, non-cured hepatitis C virus (HCV) infection. Likewise, autoimmune hepatitis will be excluded based on serological \[antinuclear antibodies (ANA), smooth muscle antibodies (SMA), and biochemical parameters AST and ALT\], patients with serological and/or biochemical findings suggestive of probable autoimmune hepatitis will be excluded
• REGISTRATION: Legal incapacity (persons in custody or under guardianship)
• REGISTRATION: Deprived of liberty subject (by judicial or administrative decision)
• REGISTRATION: Impossibility to sign the informed consent document or to adhere to the medical follow-up of the trial for geographical, social, or psychological reasons
• REGISTRATION: Any of the following because this study involves an investigational agent, the genotoxic, mutagenic and teratogenic effects of which on the developing fetus and newborn are unknown

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator
• Mayo Clinic: lead

Study Sites (1)

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Biopsy; Specimen Handling; Embolization, Therapeutic; Hepatectomy; Magnetic Resonance Spectroscopy

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

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Hemostatic Techniques; Therapeutics; Therapeutic Occlusion; Digestive System Surgical Procedures; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Scott L. Nyberg, MD, PhD

  Mayo Clinic in Rochester

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Clinical Trials Referral Office

CONTACT

855-776-0015; mayocliniccancerstudies@mayo.edu

Cancer Center Clinical Trials Referral Office

CONTACT

507-293-6386

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 21, 2026
• First Posted: May 28, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): August 1, 2028
• Last Updated: June 12, 2026

Record last verified: 2026-06

Locations

US (1)