Metastatic Melanoma, Liver Metastases
Conditions
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
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.
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
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
Sponsors
University of Wisconsin, Madison
Delcath Systems Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and Severity of Dose Limiting Toxicities (DLTs) | up to 12 weeks | 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. |
| 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) | After treatment plus follow up for 2 years (up to 4 years) | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ORR in Hepatic and Non-Hepatic Lesions | After treatment plus follow up for 2 years (up to 4 years) | 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. |
| Disease Control Rate (DCR) | After treatment plus follow up for 2 years (up to 4 years) | 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). |
| Progression Free Survival (PFS) | After treatment plus follow up for 2 years (up to 4 years) | 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. |
| Overall Survival (OS) | After treatment plus follow up for 2 years (up to 4 years) | Overall survival is defined by the date of randomization to date of death from any cause. |
| Duration of Response (DOR) | After treatment plus follow up for 2 years (up to 4 years) | 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). |
| Number of Participants with Tumor Reduction at any time | After treatment plus follow up for 2 years (up to 4 years) | — |
Countries
United States
Contacts
CONTACTCancer Connect
PRINCIPAL_INVESTIGATORVincent Ma, MD
UW Carbone Cancer Center
Outcome results
None listed