It's the “laughing so hard together” thing.

Every day, the smallest things have the potential to make the biggest difference for those who need liver-directed cancer treatment. HEPZATO KIT targets metastases in the liver and effectively treats tumors in the entire organ.

It's the “let's meet at our spot” thing.

Every day, the smallest things have the potential to make the biggest difference for those who need liver-directed cancer treatment. HEPZATO KIT targets metastases in the liver and effectively treats tumors in the entire organ.

It's the “yes, i'm here for you” thing.

Every day, the smallest things have the potential to make the biggest difference for those who need liver-directed cancer treatment. HEPZATO KIT targets metastases in the liver and effectively treats tumors in the entire organ.

It's the “just an extra pinch” thing.

Every day, the smallest things have the potential to make the biggest difference for those who need liver-directed cancer treatment. HEPZATO KIT targets metastases in the liver and effectively treats tumors in the entire organ.

It's the “laughing so hard together” thing.

Every day, the smallest things have the potential to make the biggest difference for those who need liver-directed cancer treatment. HEPZATO KIT targets metastases in the liver and effectively treats tumors in the entire organ.

It's the “let's meet at our spot” thing.

Every day, the smallest things have the potential to make the biggest difference for those who need liver-directed cancer treatment. HEPZATO KIT targets metastases in the liver and effectively treats tumors in the entire organ.

It's the “yes, i'm here for you” thing.

Every day, the smallest things have the potential to make the biggest difference for those who need liver-directed cancer treatment. HEPZATO KIT targets metastases in the liver and effectively treats tumors in the entire organ.

It's the “just an extra pinch” thing.

Every day, the smallest things have the potential to make the biggest difference for those who need liver-directed cancer treatment. HEPZATO KIT targets metastases in the liver and effectively treats tumors in the entire organ.

P
Q

Important Safety Information Including Boxed Warning

What is HEPZATO KIT?

HEPZATO KIT consists of a closed circuit of catheters and proprietary filtration technology utilized to deliver HEPZATO (melphalan) to the hepatic artery and to lower the concentration of melphalan in the blood before it is returned to systemic circulation.

HEPZATO (melphalan) for injection is a component of the HEPZATO KIT Hepatic Delivery System (HDS) for intra-arterial use. Initial U.S. approval: 1964

WARNING: SEVERE PERI-PROCEDURAL COMPLICATIONS, MYELOSUPPRESSION

See full prescribing information for complete boxed warning.

  • Severe peri-procedural complications including hemorrhage, hepatocellular injury, and thromboembolic events may occur with intra-hepatic administration of HEPZATO. Assess patients for these adverse reactions during and for 72 hours following administration of HEPZATO.
  • HEPZATO is available only through a restricted program under a Risk Evaluation and Mitigation Strategy called the HEPZATO KIT REMS.
  • Myelosuppression with resulting severe infection, bleeding, or symptomatic anemia may occur with HEPZATO. Monitor hematologic laboratory parameters and delay additional cycles of HEPZATO therapy until blood counts have improved.

INDICATIONS AND USAGE

HEPZATO is an alkylating drug indicated as a liver-directed treatment for adult patients with uveal melanoma with unresectable hepatic metastases 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 amenable to resection or radiation.

DOSAGE AND ADMINISTRATION

HEPZATO, a component of the HEPZATO KIT, is administered by intra-arterial infusion into the hepatic artery (see instructions for use [IFU]). The recommended dose is 3 mg/kg based on ideal body weight (see Table 1), with a maximum absolute dose of 220 mg during a single HEPZATO treatment. The drug is infused over 30 minutes followed by a 30-minute washout period (see IFU). Treatments should be administered every six (6) to eight (8) weeks but can be delayed until recovery from toxicities and as per clinical judgement.

DOSAGE FORMS AND STRENGTHS

For injection: HEPZATO includes 50 mg freeze-dried (lyophilized) melphalan powder per vial in five (5) single dose vials, intended for reconstitution with the supplied diluents.

CONTRAINDICATIONS

  • 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
  • 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 utilized within the HEPZATO KIT including natural rubber latex, heparin, and severe hypersensitivity to iodinated contrast not controlled by antihistamines and steroids

WARNINGS AND PRECAUTIONS

  • 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
  • Embryo-fetal toxicity: Can cause fetal harm. Advise females of reproductive potential and males with female partners of reproductive potential of the potential risk to a fetus and to use effective contraception
  • Infertility: Melphalan-based chemotherapy regimens have been reported to cause suppression of ovarian function in premenopausal women and testicular suppression in men

ADVERSE REACTIONS

Most common (≥20%) adverse reactions or laboratory abnormalities are thrombocytopenia, fatigue, anemia, nausea, musculoskeletal pain, leukopenia, abdominal pain, neutropenia, vomiting, increased alanine aminotransferase, prolonged activated partial thromboplastin time, increased aspartate aminotransferase, increased alkaline phosphatase, and dyspnea.

To report SUSPECTED ADVERSE REACTIONS, contact Delcath at 1-833-632-0458 and www.Delcath.com or FDA at 1-800-FDA-1088 or http://www.fda.gov/medwatch.

USE IN SPECIFIC POPULATIONS

  • HEPZATO should not be used in patients < 35 kg
  • Lactation: Advise not to breastfeed

Your Title Goes Here

HEPZATO KIT:
First and Only FDA-Approved Whole Liver Directed Therapy1

HEPZATO KIT is a unique treatment that delivers high-dose chemotherapy to the entire liver while limiting systemic exposure.1-3

Isolation

Isolation

Isolating the liver blood supply allows for the benefits of high-dose melphalan while reducing systemic toxicity3,4

Saturation

Saturation

A 30-minute infusion of high-dose melphalan saturates the liver, effectively delivering treatment to the entire organ1,3

Filtration

Filtration

A 30-minute washout period limits systemic drug exposure (mean [SD] filter efficiency of 82.7% [14.4%] for the total filtration period)1

HK-diagram-static

Melphalan mechanism of action1,5,6

Melphalan mechanism in action

How melphalan works

Melphalan acts by introducing interstrand cross-links into DNA. It is active against both resting and rapidly dividing tumor cells.1

You May Know Melphalan But Not Like This

HEPZATO KIT delivers the potency of high-dose melphalan directly into the liver. Melphalan causes rapid and irreversible DNA damage that results in cancer cell death.1

  • Melphalan has been approved and used in the United States since 19641

Delivering an Innovative Treatment With a Well-Trained Team

HEPZATO KIT is available only through a restricted program under a risk evaluation and mitigation strategy (REMS) called the HEPZATO KIT REMS.

Treatment with HEPZATO KIT involves training and a team approach. All procedure team members complete a REMS training. HEPZATO KIT procedure team members include2,a:

radiologist

Interventional radiologist

Leads and performs the vascular interventional procedure2

perfusionist

Perfusionist

Establishes, monitors, and controls the extracorporeal pump and veno-venous bypass circuit2
anesthesiologist

Anesthesiologist

Manages sedation, analgesia, and respiratory and cardiovascular support2

Other clinical team members involved with HEPZATO KIT treatment include the medical/surgical oncologist, pharmacist, chemotherapist, and intensivist.2

Medical/surgical oncologist

Pharmacist

Chemotherapist

Intensivist

aAll REMS materials are available at www.HEPZATOKITREMS.com or by calling the REMS coordinating center at 1-833-632-0457.

FOCUS Study Highlights

What was the FOCUS Study?

FOCUS was a multicenter, open-label trial that evaluated the efficacy and safety of melphalan delivered with the HEPZATO KIT in patients with unresectable metastatic uveal melanoma (mUM) predominately involving the liver.1

  • Primary efficacy end point: Objective response rate (ORR)1
  • Key secondary end point: Duration of response (DoR)1

More Than 1/3 of Patients Responded to Treatment With HEPZATO KIT1

ORR reported in FOCUS was 36.3% (n = 33)1

  • Complete response (CR): 7.7% (n = 7)1
  • Partial response (PR): 28.6% (n = 26)1

Median DoR in responders (n = 33) was 14 months1,c

ORR (CR or PR) in FOCUS1

Efficacy Charts

Responders in FOCUS trial (n = 33)1

14 Months

CR: Disappearance of all target lesionsa

PR: ≥30% Decrease in the sum of the long axis diameter of tumor target lesionsb

aAny pathological lymph nodes (target or nontarget) must be <10 mm in short-axis diameter. For nontarget lesions, disappearance of all nontarget lesions and normalization of tumor marker level.7

bUsing the baseline sum as reference.7

cCalculated using Kaplan-Meier method.1

FOCUS Study Design1

Study patients

95 Patients were enrolled into the HEPZATO KIT arm; 91 patients received treatment.1,a

91 of 95
Patients could have limited extrahepatic disease in the bone, subcutaneous sites, lymph nodes, or lung if the life-threatening component of the UM was in the liver. Any extrahepatic disease needed to be amenable to resection or radiation, with a defined treatment plan.1

Key exclusion criteria1

  • Metastases occupying ≥50% of the liver parenchyma
  • Unable to undergo general anesthesia
  • ECOG PS ≥2
  • Platelet count <100,000/μL
  • Absolute neutrophil count <1500/μL
  • Hemoglobin level <10 g/dL
  • Child-Pugh class B or C cirrhosis
  • Hepatitis B or C infection

ECOG PS, Eastern Cooperative Oncology Group performance status.

Treatment schedule

Patients received a dose of 3 mg/kg of melphalan using the HEPZATO KIT every 6 to 8 weeks for up to 6 treatment cycles.1,a

  • Patients received a median of 4 treatment cycles (range, 1-6 cycles)
  • The maximum of 6 treatment cycles was received by 37% of the 91 treated patients

aBased on ideal body weight (IBW; maximum total dose, 220 mg).

FOCUS trial-graphic

Want to know more about the FOCUS Study?

Visit Clinicaltrials.gov: NCT02678572

HEPZATO KIT: Demonstrated Safety and Tolerability1

Most common adverse events (>30% of patients)1

  • Nausea
  • Fatigue
  • Musculoskeletal pain
  • Abdominal pain
  • Vomiting

All adverse events observed at a frequency of >10% in patients treated with HEPZATO KIT (N = 95)1

Gastrointestional disorders
Nausea
Abdominal paina
Vomitinga
Diarrheaa
General disorders
Fatiguea
Pyrexiaa
Musculoskeletal and connective tissue disorders
Musculoskeletal paina
Groin pain
Respiratory disorders
Dyspneaa
Cougha
Nervous system disorders
Headachea
Lethargy
Dizzinessa
Injury and procedural complications
Contusion
Metabolism and nutrition disorders
Decreased appetite
Vascular disorders
Hemorrhagea
Hypotensiona
All grades, %
Gastrointestional disorders
57
39
35
17
General disorders
65
16
Musculoskeletal and connective tissue disorders
46
11
Respiratory disorders
23
15
Nervous system disorders
19
12
11
Injury and procedural complications
17
Metabolism and nutrition disorders
16
Vascular disorders
15
13
Grades 3 or 4, %
Gastrointestional disorders
0
1
0
1
General disorders
0
0
Musculoskeletal and connective tissue disorders
1
0
Respiratory disorders
2
0
Nervous system disorders
0
0
0
Injury and procedural complications
0
Metabolism and nutrition disorders
0
Vascular disorders
1
3
Gastrointestional disorders
Nausea
Abdominal pain
Vomiting
Diarrhea
General disorders
Fatigue
Pyrexia
Musculoskeletal and connective tissue disorders
Musculoskeletal paina
Groin pain
Respiratory disorders
Dyspneaa
Cougha
Nervous system disorders
Headachea
Lethargy
Dizzinessa
Injury and procedural complications
Contusion
Metabolism and nutrition disorders
Decreased appetite
Vascular disorders
Hemorrhagea
Hypotensiona
All Grades (%)
57
39
35
17
65
16
46
11
23
15
19
12
11
17
16
15
13
Grades 3 or 4 (%)
0
1
0
1
0
0
1
0
2
0
0
0
0
0
0
1
3

aRepresents a composite of multiple, related preferred terms.

Serious adverse events occurred in 45% of patients who received treatment with HEPZATO KIT1

Serious adverse events occurring in ≥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%), hypoxia (2.1%), pleural effusion (2.1%), pulmonary edema (2.1%), and deep vein thrombosis (2.1%).1

Fatal adverse events occurred in 3 patients (3.2%) who were treated with HEPZATO KIT; these included cardiac arrest, acute hepatic failure, and bacterial peritonitis and were deemed not to be related to HEPZATO KIT treatment.1,8

HEPZATO KIT treatment was permanently discontinued because of adverse events in 18% of patients, with neutropenia being the most common reason (3.2%).1

Frequently Asked Questions

What is metastatic uveal melanoma (mUM)?

Uveal melanoma (UM) is a type of cancer that arises from melanocytes in the uveal tract of the eye.9 Approximately half of all patients with UM develop metastatic disease, and the liver is involved in 90% of mUM cases.9-11 UM-related mortality is often due to complications from metastatic disease, and most patients with mUM die from liver failure.10

What does treatment with HEPZATO KIT involve?

Treatment with HEPZATO KIT involves a minimally invasive, repeatable surgical procedure that isolates the hepatic blood supply, saturates the liver with high-dose melphalan, and then filters the chemotherapy from systemic circulation to limit drug exposure (mean [SD] filter efficiency of 82.7% [14.4%] for the total filtration period)1-3

Who is an appropriate patient for HEPZATO KIT?

HEPZATO KIT is indicated for adult patients with mUM with unresectable hepatic metastases 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 amenable to resection or radiation. In the multicenter, open-label FOCUS trial in which the effects of HEPZATO KIT were studied, patients were required to have unresectable mUM, with metastasis predominantly involving the liver (liver-dominant). Limited extrahepatic disease in the bone, subcutaneous sites, lymph nodes, or lung was permitted if the life-threatening component of the UM was in the liver and the extrahepatic disease was amenable to resection or radiation and had a defined treatment plan.1

Patient eligibility for HEPZATO KIT depends on several factors, which should be determined and assessed by the treating physician.1

How can I find a healthcare setting for HEPZATO KIT?

HEPZATO KIT is available at multiple cancer centers in the United States. Use the Healthcare Setting Locator to find a treatment center near you. For more information, email medaffairs@delcath.com or call +1 833-632-0458.

Is there a treatment access program for HEPZATO KIT?

Yes. HEPZATO KIT Access is a personalized support program offered to patients, providers, and facilities while navigating the payor authorization process. Dedicated reimbursement experts will provide status updates while coverage and product access details are finalized.

Healthcare Setting Locator

Find a certified healthcare setting near you

References:

1. HEPZATO KIT. Package insert. Delcath Systems, Inc. 2023. 2. HEPZATO KIT. Instructions for use. Delcath Systems, Inc. 2023. 3. Quadri HS, Payabyab EC, Chen DJ, Figg W, Hughes MS. Percutaneous hepatic perfusion with melphalan for unresectable liver metastasis. Hepatoma Res. 2016;2:197-202. 4. Ferrucci PF, Cocorocchio E, Bonomo G, Varano GM, Della Vigna P, Orsi F. A new option for the treatment of intrahepatic cholangiocarcinoma: Percutaneous hepatic perfusion with CHEMOSAT delivery system. Cells. 2021;10(1):70.  5. Rycenga HB, Long DT. The evolving role of DNA inter-strand crosslinks in chemotherapy. Curr Opin Pharmacol. 2018;41:20-26. 6. Ramnani D. Metastatic malignant melanoma. WebPathology, LLC. Accessed November 9, 2023. https://www.webpathology.com/image.asp?case=243&n=30. 7. Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228-247. 8. Delcath Systems Inc. Data on file. 2.5 Clinical overview: Melphalan/HDS; hepatic-dominant ocular melanoma. 2022. 9. Krantz BA, Dave N, Komatsubara KM, Marr BP, Carvajal RD. Uveal melanoma: Epidemiology, etiology, and treatment of primary disease. Clin Ophthalmol. 2017;11:279-289. 10. Eschelman DJ, Gonsalves CF, Sato T. Transhepatic therapies for metastatic uveal melanoma. Semin Intervent Radiol. 2013;30(1):39-48. 11. Harbour JW. A prognostic test to predict the risk of metastasis in uveal melanoma based on a 15-gene expression profile. Methods Mol Biol. 2014;1102:427-440.

Important Safety Information Including Boxed Warning

What is HEPZATO KIT?

HEPZATO KIT consists of a closed circuit of catheters and proprietary filtration technology utilized to deliver HEPZATO (melphalan) to the hepatic artery and to lower the concentration of melphalan in the blood before it is returned to systemic circulation.

HEPZATO (melphalan) for injection is a component of the HEPZATO KIT Hepatic Delivery System (HDS) for intra-arterial use. Initial U.S. approval: 1964

WARNING: SEVERE PERI-PROCEDURAL COMPLICATIONS, MYELOSUPPRESSION

See full prescribing information for complete boxed warning.

  • Severe peri-procedural complications including hemorrhage, hepatocellular injury, and thromboembolic events may occur with intra-hepatic administration of HEPZATO. Assess patients for these adverse reactions during and for 72 hours following administration of HEPZATO.
  • HEPZATO is available only through a restricted program under a Risk Evaluation and Mitigation Strategy called the HEPZATO KIT REMS.
  • Myelosuppression with resulting severe infection, bleeding, or symptomatic anemia may occur with HEPZATO. Monitor hematologic laboratory parameters and delay additional cycles of HEPZATO therapy until blood counts have improved.

INDICATIONS AND USAGE

HEPZATO is an alkylating drug indicated as a liver-directed treatment for adult patients with uveal melanoma with unresectable hepatic metastases 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 amenable to resection or radiation.

DOSAGE AND ADMINISTRATION

HEPZATO, a component of the HEPZATO KIT, is administered by intra-arterial infusion into the hepatic artery (see instructions for use [IFU]). The recommended dose is 3 mg/kg based on ideal body weight (see Table 1), with a maximum absolute dose of 220 mg during a single HEPZATO treatment. The drug is infused over 30 minutes followed by a 30-minute washout period (see IFU). Treatments should be administered every six (6) to eight (8) weeks but can be delayed until recovery from toxicities and as per clinical judgement.

DOSAGE FORMS AND STRENGTHS

For injection: HEPZATO includes 50 mg freeze-dried (lyophilized) melphalan powder per vial in five (5) single dose vials, intended for reconstitution with the supplied diluents.

CONTRAINDICATIONS

  • 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
  • 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 utilized within the HEPZATO KIT including natural rubber latex, heparin, and severe hypersensitivity to iodinated contrast not controlled by antihistamines and steroids

WARNINGS AND PRECAUTIONS

  • 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
  • Embryo-fetal toxicity: Can cause fetal harm. Advise females of reproductive potential and males with female partners of reproductive potential of the potential risk to a fetus and to use effective contraception
  • Infertility: Melphalan-based chemotherapy regimens have been reported to cause suppression of ovarian function in premenopausal women and testicular suppression in men

ADVERSE REACTIONS

Most common (≥20%) adverse reactions or laboratory abnormalities are thrombocytopenia, fatigue, anemia, nausea, musculoskeletal pain, leukopenia, abdominal pain, neutropenia, vomiting, increased alanine aminotransferase, prolonged activated partial thromboplastin time, increased aspartate aminotransferase, increased alkaline phosphatase, and dyspnea.

To report SUSPECTED ADVERSE REACTIONS, contact Delcath at 1-833-632-0458 and www.Delcath.com or FDA at 1-800-FDA-1088 or http://www.fda.gov/medwatch.

USE IN SPECIFIC POPULATIONS

  • HEPZATO should not be used in patients < 35 kg
  • Lactation: Advise not to breastfeed