Hepzato Kit and Opdualag for Metastatic Melanoma and Liver Metastasis

Official title

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

Overview

This study is being done to see if combining HEPZATO KIT™ with nivolumab and relatlimab (Opdualag™) 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™).

Interventions

• 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.
• 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

Primary outcome measures

• Incidence and Severity of Dose Limiting Toxicities (DLTs) [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) [Time frame: After treatment plus follow up for 2 years (up to 4 years)]

Secondary outcome measures (6)

• 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

Inclusion criteria

• Histologically or cytologically confirmed metastatic melanoma with liver metastasis (LM). Liver biopsy positive for presence of melanoma metastases is required.
• 0-1 line of prior systemic therapy in the unresectable/metastatic setting - prior adjuvant anti-programmed cell death-1 (anti-PD-1) or BRAF/MEK targeted therapy is considered 1 line of prior systemic therapy if less 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• UW Hospital and Clinics — Madison

Identifiers

NCT: NCT07281924 · 2025-1424 · UW25072 · Protocol Version 6/23/26 · SMPH/MEDICINE/HEM-ONC

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗