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.
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
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
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.
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
UW Hospital and Clinics
Madison, Wisconsin, United States
RECRUITINGIncidence 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)
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.
Time frame: 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).
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Time frame: 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.
Time frame: 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.
Time frame: 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).
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)