Hepzato Kit and Opdualag for Metastatic Melanoma and Liver Metastasis

NCT07281924 | Recruiting Phase 1 DMC FDA Drug

• 4 other identifiers: 2025-1424UW25072Protocol Version 9/26/25SMPH/MEDICINE/HEM-ONC
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Metastatic Melanoma; Liver Metastases

Keywords

immunotherapy; Liver metastases; Anti-PD-1; Anti-LAG-3; Melphalan; Percutaneous Hepatic Perfusion Therapy; Liver directed therapy; Nivolumab; Relatlimab; Immune Checkpoint Inhibitors; Hepzato; Opdualag

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (6)

• ORR in Hepatic and Non-Hepatic Lesions

  After treatment plus follow up for 2 years (up to 4 years)

• Disease Control Rate (DCR)

  After treatment plus follow up for 2 years (up to 4 years)

• Progression Free Survival (PFS)

  After treatment plus follow up for 2 years (up to 4 years)

• Overall Survival (OS)

  After treatment plus follow up for 2 years (up to 4 years)

• Duration of Response (DOR)

  After treatment plus follow up for 2 years (up to 4 years)

Study Arms (1)

Participants with Metastatic Melanoma

EXPERIMENTAL

Drug: Nivolumab and Relatlimab; Device: Melphalan

Interventions

Nivolumab and Relatlimab DRUG

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.

Also known as: Opdualag

Participants with Metastatic Melanoma

Melphalan DEVICE

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

Also known as: HEPZATO KIT

Participants with Metastatic Melanoma

Eligibility Criteria

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

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• Delcath Systems Inc.: collaborator
• University of Wisconsin, Madison: lead

Study Sites (1)

UW Hospital and Clinics

Madison, Wisconsin, 53792, United States

RECRUITING

MeSH Terms

Conditions

Melanoma

Interventions

Nivolumab; relatlimab; Opdualag

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Vincent Ma, MD

  UW Carbone Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Cancer Connect

CONTACT

800-622-8922; clinicaltrials@cancer.wisc.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Five patients will be treated first. If at least two achieve an objective response and no more than two experience a DLT, an additional ten patients will be enrolled, giving a total sample of fifteen. If the first 5 participants records three or more DLTs, or one or fewer responses, the trial will halt.

Study Record Dates

• First Submitted: December 4, 2025
• First Posted: December 15, 2025
• Study Start: May 1, 2026
• Primary Completion (Estimated): December 1, 2030
• Study Completion (Estimated): December 1, 2030
• Last Updated: May 5, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• 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

Locations

US (1)