This Phase 2 study evaluates the efficacy and safety of sequential treatment with percutaneous hepatic perfusion (PHP) using melphalan/HDS followed by tebentafusp in patients with metastatic uveal melanoma (mUM) with isolated liver metastases. The rationale is that PHP enhances antigen release and immunomodulation, potentially sensitizing tumors to tebentafusp in HLA-A\*02:01-positive patients.
Patient is ≥18 years of age on the day of signing informed consent.
ECOG performance status of 0 or 1.
Histologically or cytologically confirmed liver metastasis of uveal melanoma.
HLA-A*02:01 positive status.
Life expectancy of less than 6 months.
More than 50% of the liver volume replaced by tumor as measured by MRI.
Extrahepatic disease as measured by CT of thorax abdomen and pelvis. (See inclusion criteria #10 above for limited treatable extrahepatic disease.)
History of congestive heart failure, active cardiac conditions, including unstable coronary syndromes (unstable or severe angina, recent myocardial infarction), significant arrhythmias and severe valvular disease that precludes the use of general anesthesia.
Single group
Melphalan/HDS (Percutaneous Hepatic Perfusion)
Drug3 mg/kg ideal body weight (max 220 mg) infused via hepatic artery catheter.
Tebentafusp
Drug20 mcg IV day 1, 30 mcg day 8, 68 mcg day 15, then weekly thereafter.
Progression Free Survival (PFS)
PFS will be studied as time-to-event defined by the first documented disease progression or death due to any cause, whichever occurs first, from the start date of the study treatment. PFS will be determined based on tumor assessment (RECIST version 1.1 criteria).
Objective Response Rate (ORR)
ORR defined as the percentage of patients achieving a confirmed complete or partial response, as defined by RECIST version 1.1 criteria.
Clinical Benefit Rate (CBR)
CBR defined as the percentage of patients achieving confirmed SD at 26 weeks, OR any confirmed CR or PR. As defined by RECIST version 1.1 criteria.
Hepatic PFS (hPFS)
hPFS is defined as the time-to-event defined by the first documented disease progression in the liver or death due to any cause, whichever occurs first, from the start date of the study treatment. hPFS will be determined based on tumor assessment (RECIST version 1.1 criteria).
Overall Survival (OS)
OS is calculated as the time-to-event defined by death due to any cause from the start date of the study treatment.
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H. Lee Moffitt Cancer Center and Research Institute
Lead sponsor
Delcath Systems Inc.
Collaborator
