The Hepzato Kit (melphalan/Hepatic Delivery System) is used to treat metastatic uveal melanoma (mUM) that has hepatic metastasis. The Hepzato Kit delivers melphalan, a long-approved chemotherapy treatment, directly to the liver through a novel device delivery system called the Hepatic Delivery System (HDS). This means the medicine goes directly into the liver to treat cancer while limiting the amount of Hepzato reaching the rest of the body, which reduces side effects and toxicity.

Hepzato Kit can be used for adult patients with uveal melanoma with hepatic metastases that are unable to be removed, affecting less than 50% of the liver, and no extrahepatic disease or extrahepatic disease limited to the bone, lymph nodes, subcutaneous tissues, or lung that is able to be removed or treated with radiation.

Melphalan, the active ingredient in Hepzato Kit, is from the drug class Alkylating agents.

Hepzato Kit received FDA approval on August. 14, 2023, approval was based on positive results from the FOCUS Study (NCT02678572), which was a Phase 3, single-arm, multicenter, open-label study. How effective the treatment was, was measured by objective response rate (ORR) and duration of response (DoR), ORR was 36.3%, and the median DoR was 14 months.

What is metastatic uveal melanoma?

Uveal melanoma is a very rare form of cancer that affects melanocytes in the eye. Even though surgical or radiation therapy of the primary tumor is generally successful, approximately half of all patients the uveal melanoma will move to another part of the body (metastatic disease). Most often, uveal melanoma will occur in the liver (~90% of patients) and less commonly in the lungs and bones. The treatment of liver metastases is critical since liver failure is most often the cause of death for patients with metastatic uveal melanoma. When uveal melanoma spreads to the liver, it is often lots of small nodules throughout the whole liver. The Hepzato Kit treats the entire liver, and most patients are able to undergo multiple treatments.

Hepzato can cause severe side effects, including severe peri-procedural complications and myelosuppression. See full prescribing information for a complete boxed warning.

Severe peri-procedural complications, including hemorrhage, hepatocellular injury, and thromboembolic events, may happen with intra-hepatic administration of this medicine. Assess patients for these side effects during and for 72 hours following the administration of this medicine.

Myelosuppression with resulting severe infection, bleeding, or symptomatic anemia may occur with this medicine. Monitor blood tests and delay additional cycles of therapy until blood counts have improved.

Hepzato is available only through a restricted program under a Risk Evaluation, and Mitigation Strategy called the Hepzato Kit REMS.

Hypersensitivity reactions, including anaphylaxis, have occurred in patients who received an intravenous (IV) formulation of melphalan. Immediately terminate hepatic arterial melphalan infusion for hypersensitivity reactions and administer supportive care. 

Gastrointestinal disturbances such as nausea and vomiting, abdominal pain, and diarrhea are common. 

Carcinogenic/Mutagenic effects: Secondary malignancies, including acute nonlymphocytic leukemia, myeloproliferative syndrome, and carcinoma, have been reported in patients with cancer treated with alkylating drugs (including melphalan). Melphalan has been shown to cause chromatid or chromosome damage in humans. 

Hepzato is given as a procedure by your healthcare team. It is administered using the Hepatic Delivery System (HDS). This is when catheters (tubing) are placed through the skin (percutaneously) to the liver artery, which is temporarily isolated from the body’s circulatory system. During this time, a 30-minute infusion of the melphalan passes directly into the liver. The blood is then filtered as it leaves the liver, removing melphalan from the blood before it is returned back into the patient. 

Hepzato (melphalan) for injection must only be administered with the HDS device supplied with the Hezatp Kit and components specified by Delcath Systems, Inc.

Hepzato is administered by infusion into the hepatic artery every 6 to 8 weeks for up to 6 total infusions. 

The dose is based on ideal body weight (IBW) at 3mg/kg with a maximum of 220mg during a single treatment. See Full Prescribing Information for more details.
The dose may be reduced due to side effects.

Hepzato should not be used if:

• Active intracranial metastases or brain lesions with a propensity to bleed. 
• Liver failure, portal hypertension, or known varices at risk for bleeding.
• Surgery or medical treatment of the liver in the previous 4 weeks.
• Uncorrectable coagulopathy.
• Active cardiac conditions including, but not limited to, unstable coronary syndromes (unstable or severe angina or myocardial infarction), worsening or new-onset congestive heart failure, significant arrhythmias, or severe valvular disease. 
• History of allergies or known hypersensitivity to melphalan or a component or material used within the Hepzato Kit, including natural rubber latex, heparin, and severe hypersensitivity to iodinated contrast not controlled by antihistamines and steroids.
• Hepzato should not be used in patients weighing less than 35 kg. 

Before receiving Hepzato Kit?

You tell your healthcare professional if you are allergic to the melphalan or any ingredients contained in this medicine or the Hepzato Kit click here for a full list of ingredients.

Pregnancy

Hepzato Kit can cause fetal harm.

Females who are able to become pregnant should use effective contraception while using this medicine and for  6 months  after the last dose, as there is a potential risk to a fetus if using this medicine.

Males with females partners who are able to become pregnant should use effective contraception while using this medicine and for 3 months after the last dose, as there is a potential risk to a fetus if using this medicine.

Infertility. In both females and males of reproductive potential, there is a risk of infertility. Melphalan-based chemotherapy may cause suppression of ovarian function in premenopausal women and testicular suppression in men.

Breastfeeding

Women should not breastfeed during treatment with Hepzato and for one week after the last dose.

Common Hepzato Kit side effects

Most common side effects or blood test changes that affected 20% or more of patients are thrombocytopenia (65%), tiredness (65%), low iron levels (63%), nausea (57%), muscle and bone pain (46%),  low white blood cells (46%), abdominal pain (39%), neutropenia (35%), vomiting (35%), increased alanine aminotransferase (32%), prolonged activated partial thromboplastin time (28%), increased aspartate aminotransferase (28%), increased blood alkaline phosphatase (27%), and difficulty breathing (23%). 

Serious Hepzato Kit side effects

Serious side effects happened in 45% of patients who received this medicine. Serious side effects that occurred in more than 2% of patients were

• thrombocytopenia (10%)
• neutropenia (8%) 
• febrile neutropenia (7%) 
• platelet count decreased (6%) 
• leukopenia (4.2%) 
• cardiac arrest (3.2%) 
• neutrophil count decreased (2.1%) 
• low oxygen levels (2.1%) 
• pleural effusion (2.1%) 
• pulmonary edema (2.1%)
• deep vein thrombosis (2.1%). 

Fatal side effects happened in 3 (3.2%) patients in a clinical trial who were treated with this medicine; these included cardiac arrest, acute hepatic failure, and bacterial peritonitis.