Hepzato Kit and Opdualag for Metastatic Melanoma and Liver Metastasis

A Phase 1b/2 Trial Evaluating the Safety, Tolerability, and Preliminary Efficacy of Melphalan Percutaneous Hepatic Perfusion Therapy (HEPZATO KIT™) With Nivolumab and Relatlimab (Opdualag) in Patients With Metastatic Melanoma and Liver Metastasis

This study is being done to see if combining HEPZATO KIT™ with nivolumab and relatlimab (Opdualag™) in the first line setting in patients with metastatic melanoma with liver metastasis is safe, tolerable, and will have a synergistic effect leading to improved clinical outcomes compared to the historic cohort of patients with liver metastasis treated with combination immune checkpoint inhibitor therapy.

Study Overview

• Status: Recruiting
• Conditions: Metastatic Melanoma; Liver Metastases
• Intervention / Treatment: Drug: Nivolumab and Relatlimab; Device: Melphalan

Detailed Description

Co-Primary Objectives

• To evaluate the safety and tolerability of HEPZATO KIT™ in combination with nivolumab and relatlimab (Opdualag™) in subjects with metastatic melanoma and liver metastasis (LM).
• To evaluate the preliminary systemic efficacy of HEPZATO KIT™ in combination with nivolumab and relatlimab (Opdualag™), as measured by objective response rate (ORR), in subjects with metastatic melanoma and LM.

Secondary Objectives

• To evaluate the preliminary systemic efficacy of HEPZATO KIT™ in combination with nivolumab and relatlimab (Opdualag™), as measured by ORR, in both hepatic and non-hepatic target lesions in subjects with metastatic melanoma and LM.
• To evaluate the disease control rate (DCR) in subjects with metastatic melanoma and LM receiving HEPZATO KIT™ in combination with nivolumab and relatlimab (Opdualag™).
• To evaluate the PFS in subjects with metastatic melanoma and LM receiving HEPZATO KIT™ in combination with nivolumab and relatlimab (Opdualag™).
• To evaluate the overall survival (OS) in subjects with metastatic melanoma and LM receiving HEPZATO KIT™ in combination with nivolumab and relatlimab (Opdualag™).
• To evaluate the duration of response (DOR) in subjects with metastatic melanoma and LM receiving HEPZATO KIT™ in combination with nivolumab and relatlimab (Opdualag™).
• To evaluate the tumor reduction at any time during treatment in subjects with metastatic melanoma and LM receiving HEPZATO KIT™ in combination with nivolumab and relatlimab (Opdualag™).

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Cancer Connect; Phone Number: 800-622-8922; Email: clinicaltrials@cancer.wisc.edu

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • Recruiting
      • UW Hospital and Clinics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically or cytologically confirmed metastatic melanoma with liver metastasis (LM). Liver biopsy positive for presence of melanoma metastases is required.
• Systemic treatment naïve in the unresectable/metastatic setting - prior adjuvant anti-programmed cell death-1 (anti-PD-1) and BRAF/MEK targeted therapy is allowed but must be greater than 6 months from the last treatment.
• Evaluable/measurable disease according to RECIST v1.1.
• Demonstrate adequate organ function; all screening labs to be obtained within 28 days prior to registration.
• Patients must weigh greater than or equal to 35 kilograms (due to possible size limitations with respect to percutaneous catheterization of the femoral artery and vein using the Delcath Hepatic Delivery System).

Exclusion Criteria:

• Prior treatment with HEPZATO KIT™ or nivolumab and relatlimab (Opdualag™)
• Radiotherapy is permitted within 30 days prior to C1D1 as long as radiation is given with palliative intent and towards a non-target lesion.
• History of hypersensitivity or treatment discontinuation due to grade 3+ immune-related adverse events (irAEs) from prior anti-PD-(L)1 therapy. Patients who are able to successfully resume immune checkpoint therapy without recurrence of grade 3 irAEs are eligible to participate.
• Symptomatic or uncontrolled brain metastases, leptomeningeal disease, or spinal cord compression not definitively treated with surgery or radiation.
• Prednisone use greater than or equal to 10 mg/d or equivalent
• Organ transplant recipients

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Participants with Metastatic Melanoma

Drug: Nivolumab and Relatlimab; Relatlimab is a human IgG4 LAG-3 blocking antibody. Nivolumab is a human IgG4 PD-1 blocking antibody. Nivolumab 480 mg and relatlimab 160 mg in a fixed-dose combination will be administered on Day 1 of each 28-day cycle that the participant is on treatment and will be given for up to 2 years from start of treatment.; Other Names: Opdualag; Device: Melphalan; The recommended HEPZATO dose is 3 mg/kg based on ideal body weight (IBW), infusion every 6 to 8 weeks for up to 2 total infusions; Other Names: HEPZATO KIT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and Severity of Dose Limiting Toxicities (DLTs)	A DLT is defined as any grade 4+ non-hematologic event lasting greater than 3 days (despite appropriate medical management) considered possibly related to study treatment (HEPZATO KIT™ or Opdualag™) within 12 weeks of Cycle 1 Day 1.	up to 12 weeks
Incidence of Treatment-Emergent Adverse Events		up to 2 years
Incidence of Serious Treatment-Emergent Adverse Events		up to 2 years
Number of Participants that Discontinue Treatment due to Adverse Events		up to 2 years
Overall Response Rate (ORR)	The objective response rate is the proportion of all participants with confirmed Partial Response (PR) or Complete Response (CR) according to RECIST 1.1, from the start of treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the start of treatment).	After treatment plus follow up for 2 years (up to 4 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR in Hepatic and Non-Hepatic Lesions	The proportion of all participants with confirmed PR or CR according to RECIST 1.1, from the start of treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the start of treatment) in Hepatic and Non-Hepatic Target Lesions.	After treatment plus follow up for 2 years (up to 4 years)
Disease Control Rate (DCR)	The disease control rate is the proportion of all subjects with SD for 8 weeks, or PR, or CR according to RECIST 1.1, from the start of treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the start of treatment).	After treatment plus follow up for 2 years (up to 4 years)
Progression Free Survival (PFS)	A measurement from the date of randomization until the criteria for disease progression is met as defined by RECIST 1.1 or death occurs. Participants who have not progressed will be right-censored at the date of the last disease evaluation.	After treatment plus follow up for 2 years (up to 4 years)
Overall Survival (OS)	Overall survival is defined by the date of randomization to date of death from any cause.	After treatment plus follow up for 2 years (up to 4 years)
Duration of Response (DOR)	Duration of overall response-the period measured from the time that measurement criteria are met for complete or partial response (whichever status is recorded first) until the date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since treatment started).	After treatment plus follow up for 2 years (up to 4 years)
Number of Participants with Tumor Reduction at any time		After treatment plus follow up for 2 years (up to 4 years)

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Collaborators: Delcath Systems Inc.
• Investigators: Principal Investigator: Vincent Ma, MD, UW Carbone Cancer Center

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): December 1, 2030
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: December 4, 2025
• First Submitted That Met QC Criteria: December 4, 2025
• First Posted (Actual): December 15, 2025

Study Record Updates

• Last Update Posted (Actual): May 29, 2026
• Last Update Submitted That Met QC Criteria: May 28, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: immunotherapy; Nivolumab; Anti-PD-1; Immune Checkpoint Inhibitors; Relatlimab; Melphalan; Liver metastases; Liver directed therapy; Anti-LAG-3; Percutaneous Hepatic Perfusion Therapy; Hepzato; Opdualag
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Skin Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Skin and Connective Tissue Diseases; Melanoma; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Nivolumab; relatlimab; Opdualag
• Other Study ID Numbers: 2025-1424; SMPH/MEDICINE/HEM-ONC (Other Identifier: UW Madison); UW25072 (Other Identifier: OnCore ID); Protocol Version 9/26/25 (Other Identifier: UW Madison)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Researchers must have local IRB approval for their study that is to include study of the biospecimens and accompanying data. Release of biospecimens to non-UW researchers will be performed according to all UW regulatory policies. Tissue (including blood) specimen as part of this research will be primarily stored at UW and may be sent to an outside lab/facility to achieve the objectives of the study. No study data or patient health information will be shared with a third party.
• IPD Sharing Access Criteria: Researchers who are doing biomedical research may apply to the PI for access to blood and tissue (no patient identifiers on tubes or slides). Only de-identified information will be released with the specimens
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No