RecruitingInterventionalPhase 1/Phase 2

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

NCT ID: NCT07281924Sponsor: University of Wisconsin, MadisonLast updated: 2026-05-29

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.

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™).

Arms & interventions

DrugNivolumab 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.
DeviceMelphalan
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

Outcome measures

Primary

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.
Time frame: up to 12 weeks
Incidence of Treatment-Emergent Adverse Events
Time frame: up to 2 years
Incidence of Serious Treatment-Emergent Adverse Events
Time frame: up to 2 years
Number of Participants that Discontinue Treatment due to Adverse Events
Time frame: 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).
Time frame: After treatment plus follow up for 2 years (up to 4 years)

Secondary

ORR in Hepatic and Non-Hepatic Lesions
Time frame: After treatment plus follow up for 2 years (up to 4 years)
Disease Control Rate (DCR)
Time frame: After treatment plus follow up for 2 years (up to 4 years)
Progression Free Survival (PFS)
Time frame: After treatment plus follow up for 2 years (up to 4 years)
Overall Survival (OS)
Time frame: After treatment plus follow up for 2 years (up to 4 years)
Duration of Response (DOR)
Time frame: After treatment plus follow up for 2 years (up to 4 years)
Number of Participants with Tumor Reduction at any time
Time frame: After treatment plus follow up for 2 years (up to 4 years)

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No

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 locations (1)

UW Hospital and Clinics

Madison, Wisconsin, 53792

Recruiting