Delcath Systems Doses First Patient in Phase 2 Trial of HEPZATO for Liver-Dominant Metastatic Breast Cancer
Delcath Systems, an interventional oncology company focused on developing innovative treatments for primary and metastatic liver cancers, has announced a significant milestone in its clinical development program with the dosing of the first patient in its global Phase 2 clinical trial evaluating HEPZATO™ in combination with standard-of-care (SOC) therapy for patients with liver-dominant metastatic breast cancer (mBC).
The first patient was treated at the European Institute of Oncology (IEO) in Milan, Italy, marking the official start of patient treatment in the international study. The trial, known as DELUMA (ClinicalTrials.gov Identifier: NCT06875128), is designed to evaluate whether combining HEPZATO with existing systemic therapies can improve outcomes for patients whose HER2-negative metastatic breast cancer has spread predominantly to the liver after previous treatment options have failed.
The study represents another important step in Delcath’s broader strategy to expand the clinical use of HEPZATO beyond its current applications and address significant unmet medical needs among patients with advanced cancers involving the liver.
Addressing a Major Challenge in Metastatic Breast Cancer
Breast cancer remains one of the most frequently diagnosed cancers worldwide, and although advances in treatment have significantly improved survival for many patients, metastatic disease continues to present substantial clinical challenges.
When breast cancer spreads beyond the breast and nearby lymph nodes, it can metastasize to several organs, including the bones, lungs, brain, and liver. Among these sites, liver metastases are associated with particularly poor outcomes because they can compromise essential liver function while limiting the effectiveness of many systemic therapies.
Patients with liver-dominant metastatic breast cancer often experience progressive disease despite multiple lines of treatment. Once standard therapies lose effectiveness, physicians have relatively few options capable of controlling liver tumors while maintaining quality of life.
Delcath hopes that HEPZATO, when combined with established systemic treatments, may provide a new liver-directed therapeutic strategy capable of improving disease control in this difficult-to-treat patient population.
Launch of the DELUMA Phase 2 Trial
The DELUMA study is a randomized, controlled, international Phase 2 clinical trial designed to compare HEPZATO plus standard-of-care therapy with standard-of-care treatment alone.
Researchers will enroll approximately 90 patients diagnosed with HER2-negative liver-dominant metastatic breast cancer whose disease has progressed following previous lines of therapy.
Participants will be randomly assigned to receive either:
- HEPZATO combined with physician-selected standard-of-care therapy
- Standard-of-care therapy alone
The study is expected to be conducted across more than 20 leading cancer centers located throughout the United States and Europe, allowing investigators to evaluate the treatment across diverse healthcare systems and patient populations.
The initiation of patient dosing at the European Institute of Oncology signals the beginning of active enrollment and treatment as additional sites prepare to recruit eligible participants.
Understanding HEPZATO
HEPZATO is Delcath’s proprietary liver-directed treatment platform designed to deliver high-dose chemotherapy directly to the liver while reducing systemic exposure.
Unlike conventional intravenous chemotherapy, which circulates throughout the body, HEPZATO enables physicians to administer concentrated chemotherapy directly into the hepatic circulation.
During treatment, a specialized delivery system temporarily isolates the liver’s blood flow while blood exiting the liver undergoes filtration before returning to the patient’s circulation.
This regional treatment approach offers several potential advantages:
- Delivery of higher concentrations of chemotherapy directly to liver tumors
- Reduced exposure of healthy tissues to chemotherapy
- Potential improvement in tumor response within the liver
- Preservation of systemic treatment options
- Reduced systemic toxicity compared with conventional dosing approaches
By targeting the liver specifically, HEPZATO aims to maximize treatment effectiveness where metastatic disease is most extensive while minimizing adverse effects elsewhere in the body.
Standard-of-Care Therapies Included in the Trial
Patients enrolled in DELUMA will continue receiving recognized systemic treatments for metastatic breast cancer in addition to HEPZATO where applicable.
The physician-selected standard-of-care options include:
Eribulin
Eribulin is a microtubule inhibitor commonly used in patients with metastatic breast cancer who have previously received anthracycline- and taxane-based chemotherapy. It has demonstrated activity in heavily pretreated patients and remains an important later-line treatment option.
Vinorelbine
Vinorelbine is a chemotherapy agent that interferes with cell division by disrupting microtubule formation. It is widely used for advanced breast cancer and may be administered as monotherapy or in combination with other agents.
Capecitabine
Capecitabine is an oral chemotherapy that converts into fluorouracil (5-FU) inside tumor tissue. It is frequently prescribed for metastatic breast cancer and provides patients with the convenience of oral administration while maintaining established efficacy.
Allowing physicians to choose among these therapies reflects real-world clinical practice while ensuring patients continue receiving recognized systemic treatment.
Primary and Secondary Study Objectives
The primary objective of the DELUMA trial is to determine whether adding HEPZATO improves hepatic progression-free survival (hPFS).
Hepatic progression-free survival measures the length of time patients remain free from progression of tumors within the liver.
Because liver metastases often become the primary driver of disease progression and mortality in this patient population, delaying hepatic progression represents an important clinical goal.
In addition to the primary endpoint, investigators will evaluate several important secondary outcomes, including:
- Overall progression-free survival
- Overall response rate
- Disease control rate
- Overall survival
- Safety and tolerability
- Treatment-related adverse events
Together, these endpoints will provide a comprehensive assessment of whether liver-directed therapy offers meaningful clinical benefits beyond conventional systemic treatment alone.
Why Liver-Dominant Disease Requires Specialized Approaches
For many patients with metastatic breast cancer, liver involvement becomes the most serious aspect of the disease.
Although cancer may exist elsewhere in the body, progressive liver metastases frequently determine overall prognosis because the liver performs numerous essential metabolic, detoxification, and synthetic functions.
As liver tumors enlarge, patients may develop:
- Liver dysfunction
- Fatigue
- Weight loss
- Abdominal discomfort
- Elevated liver enzymes
- Jaundice
- Reduced tolerance for additional systemic therapies
Consequently, controlling liver disease has become an increasingly important focus in metastatic oncology.
Regional therapies capable of targeting liver tumors directly may offer benefits beyond those achieved with systemic chemotherapy alone.
Significant Unmet Medical Need
According to Delcath’s estimates, approximately 7,000 patients each year in the United States have HER2-negative metastatic breast cancer with liver metastases and eventually become candidates for third-line treatment.
These patients often have exhausted multiple standard therapies before reaching this stage of disease.
Unfortunately, treatment options become increasingly limited as tumors develop resistance to available medications.
Many patients continue experiencing progression within the liver despite receiving chemotherapy, endocrine therapy, targeted agents, or antibody-drug conjugates.
This unmet need has motivated researchers to investigate complementary liver-directed treatment strategies capable of extending disease control.
Delcath believes HEPZATO may represent one such opportunity.
Building on Previous Clinical Experience
The current Phase 2 breast cancer study builds upon Delcath’s growing clinical experience using HEPZATO in other liver-related malignancies.
The company has already achieved commercial success treating patients with metastatic uveal melanoma, a rare cancer originating in the eye that frequently spreads to the liver.
Patients with metastatic uveal melanoma often develop liver-dominant disease similar to many individuals with advanced breast cancer.
Clinical experience gained from treating these patients has provided important insights regarding patient selection, treatment delivery, procedural safety, and physician education.
Delcath now hopes to translate that expertise into additional cancer indications where liver metastases significantly influence patient outcomes.
Encouraging Real-World Evidence
Company leadership also highlighted encouraging findings presented during the ESMO Breast Cancer 2026 meeting.
According to Delcath, real-world evidence presented at the conference demonstrated promising efficacy signals supporting continued investigation of liver-directed therapy in metastatic breast cancer.
Although randomized controlled trials remain necessary to confirm clinical benefit, these earlier observations contributed to the decision to expand HEPZATO’s clinical evaluation through the DELUMA study.
Real-world evidence increasingly complements traditional clinical trials by providing insights into treatment performance under routine clinical practice.
The Phase 2 trial is expected to generate more rigorous evidence regarding efficacy and safety through its randomized controlled design.
Expanding Physician Education and Clinical Adoption
Beyond conducting clinical research, Delcath is working to increase physician awareness regarding liver-directed therapies.
As HEPZATO expands into additional oncology indications, physician education becomes increasingly important.
The company reports ongoing efforts to:
- Strengthen engagement with participating clinical sites
- Educate oncologists regarding liver-directed treatment approaches
- Improve identification of appropriate patients
- Support trial enrollment
- Expand institutional expertise in regional hepatic therapies
These initiatives aim to facilitate broader clinical adoption should future studies demonstrate meaningful patient benefit.
Leadership Perspective
Gerard Michel, Chief Executive Officer of Delcath Systems, described dosing the first patient as an important milestone in the company’s ongoing clinical development strategy.
According to Michel, the initiation of the Phase 2 trial reflects Delcath’s commitment to expanding HEPZATO beyond metastatic uveal melanoma into additional cancers characterized by liver-dominant disease.
He noted that encouraging efficacy signals observed in previously presented real-world evidence, together with the company’s commercial experience, have strengthened confidence in continuing clinical evaluation.
Michel also emphasized the company’s focus on building relationships with treatment centers, increasing physician familiarity with liver-directed therapy, and identifying appropriate patients who may benefit from participation in the study.
He expressed optimism regarding the progress already being made and indicated that Delcath looks forward to further evaluating HEPZATO’s potential to address significant unmet needs across multiple oncology indications.
The dosing of the first patient in the DELUMA Phase 2 clinical trial marks an important advancement in Delcath Systems’ efforts to broaden the application of HEPZATO as a liver-directed therapy for patients with advanced cancers. By combining HEPZATO with established systemic treatments, the company aims to determine whether targeted hepatic chemotherapy can improve outcomes for individuals with HER2-negative metastatic breast cancer whose disease is predominantly confined to the liver after previous therapies have failed.
With approximately 90 patients expected to enroll across more than 20 sites in the United States and Europe, the study will provide valuable data on hepatic progression-free survival, overall response, disease control, and overall survival. If successful, the DELUMA trial could establish HEPZATO as a novel therapeutic option for thousands of patients each year who face limited treatment choices after standard therapies lose effectiveness, while reinforcing the growing role of liver-directed interventions in the management of metastatic cancer.
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