Delcath Systems, Inc. has dosed the first patient at the European Institute of Oncology in Milan, Italy, in the global Phase 2 DELUMA trial evaluating HEPZATO with standard chemotherapy for liver-dominant HER2-negative metastatic breast cancer. The randomized study will compare the liver-directed treatment followed by physician-selected chemotherapy against chemotherapy alone in approximately 90 previously treated patients.
DELUMA represents more than another early clinical milestone for the Nasdaq-listed interventional oncology company. It moves HEPZATO into an actively enrolling randomized trial in a cancer population considerably larger and more clinically diverse than metastatic uveal melanoma, the indication for which the drug-device combination is currently approved in the United States.
The development programme is also testing a broader therapeutic proposition. Rather than selecting treatment solely according to the breast cancer’s molecular subtype, Delcath is attempting to address the organ that has become the dominant source of disease burden. That strategy may be relevant when progression in the liver poses the most immediate threat, even though metastatic disease may also be present elsewhere.
Why does liver-dominant progression create a distinct treatment opportunity in metastatic breast cancer?
Patients entering DELUMA must have HER2-negative metastatic breast cancer in which most of the tumour burden is located in the liver, or the liver disease represents the life-threatening component of their cancer. Liver involvement cannot exceed 50% of the organ, measurable hepatic disease must be present, and any cancer outside the liver must be limited enough for investigators to consider the hepatic metastases the principal clinical concern.
That definition is central to the trial’s rationale. Systemic breast cancer therapies are designed to treat cancer throughout the body, but their effectiveness can become constrained when one organ progresses more aggressively than other disease sites. In these cases, gaining stronger control over the liver may potentially delay clinical deterioration and extend the period during which systemic treatment remains useful.
HEPZATO approaches the problem by delivering a high concentration of melphalan through the hepatic artery while the liver’s venous blood is temporarily isolated from the wider circulation. Blood leaving the liver passes through an extracorporeal filtration system intended to remove much of the chemotherapy before it is returned to the patient.
The concept allows the liver to receive a melphalan dose that could not ordinarily be administered systemically. It also makes HEPZATO fundamentally different from another intravenous breast cancer medicine. The product combines chemotherapy, catheter-based intervention, blood filtration, anaesthesia and hospital infrastructure in a single treatment procedure.
DELUMA must nevertheless demonstrate that stronger control inside the liver translates into a meaningful clinical advantage. A therapy can delay hepatic progression without adequately controlling cancer elsewhere, particularly in a heterogeneous metastatic breast cancer population. That is why the trial’s secondary measures, including overall progression-free survival, objective response rate, disease control rate and overall survival, may prove as important to the programme’s future as the primary hepatic progression-free survival endpoint.
How does DELUMA improve on the limited evidence already available for hepatic perfusion?
The decision to proceed into a randomized study follows retrospective European experience with melphalan percutaneous hepatic perfusion in liver-dominant metastatic breast cancer. An analysis presented at the ESMO Breast Cancer Congress 2026 included 15 heavily pretreated patients who had received a median of four previous systemic therapy lines.
Nine of the 15 patients experienced a hepatic partial response, although three patients were not evaluable for tumour response. The signal was encouraging enough to support further investigation, but the small, retrospective dataset cannot establish whether hepatic perfusion performs better than another course of chemotherapy.
The survival findings were also difficult to interpret. Median overall survival from the first hepatic perfusion procedure was six months, while individual outcomes ranged from only a few weeks to more than six years. Such variation can reflect differences in tumour biology, disease burden, treatment selection and subsequent therapies rather than the effect of the procedure alone.
DELUMA addresses some of those uncertainties through a randomized, controlled design. Patients will be assigned to HEPZATO followed by standard treatment or to standard treatment alone. The chemotherapy options are eribulin, vinorelbine or capecitabine, selected by the treating physician according to the patient’s condition and prior treatment history.
Patients assigned to the experimental arm may undergo as many as two HEPZATO procedures, with standard chemotherapy administered after each procedure. Scans are expected approximately every eight weeks, providing a structured comparison of disease control between the two groups.
The open-label design remains a limitation because investigators and patients will know which treatment has been administered. Hepatic progression-free survival is also an organ-specific endpoint rather than a direct measure of how long patients live. A statistically positive result would therefore need to be examined alongside overall disease progression, treatment exposure, safety, subsequent therapy and survival.
Why could HEPZATO’s procedural demands influence adoption as much as the clinical results?
HEPZATO requires far more infrastructure than conventional outpatient chemotherapy. The procedure involves general anaesthesia, hepatic arterial catheterisation, temporary vascular isolation of the liver, extracorporeal blood filtration and coordinated post-procedure monitoring.
Suitable treatment centres need trained interventional radiologists, anaesthesia teams, perfusion specialists, oncology staff and access to hospital resources capable of managing potential bleeding, cardiovascular instability and blood-count suppression. Patient selection must also account for cardiac function, pulmonary health, coagulation status, portal hypertension, liver function and the ability to tolerate general anaesthesia.
These requirements create a higher adoption threshold than prescribing another systemic drug. Even when clinical efficacy is persuasive, referral pathways must connect breast oncologists with specialised interventional oncology centres. Procedures must be scheduled without creating lengthy interruptions in systemic treatment, and hospitals must determine whether expected patient volumes justify training and maintaining the necessary teams.
Delcath has already built part of this infrastructure through the commercial launch of HEPZATO in metastatic uveal melanoma. The company reported 29 active treatment centres during the first quarter of 2026, providing an existing network that may support additional clinical indications.
However, the metastatic breast cancer referral pathway is different. Breast oncologists manage a much larger and more molecularly segmented patient population, while many HEPZATO centres have developed their experience through ocular oncology and melanoma programmes. Identifying the relatively narrow subgroup with liver-dominant, HER2-negative disease will require education, imaging review and coordination across disciplines.
Dosing the first DELUMA patient in Milan demonstrates that the study can begin within an experienced European hepatic perfusion environment. The larger operational test will be whether Delcath can activate more than 20 planned sites across the United States and Europe and maintain consistent enrolment in a highly selected later-line population.
What safety trade-offs will clinicians examine when HEPZATO is added before chemotherapy?
HEPZATO carries boxed warnings in its approved metastatic uveal melanoma indication for severe procedure-related complications and myelosuppression. Potential complications include haemorrhage, liver injury and thromboembolic events, while reduced blood-cell counts can lead to infection, bleeding or symptomatic anaemia.
The earlier metastatic breast cancer experience reinforces the need for close safety assessment. In the 15-patient retrospective cohort, two-thirds of patients required blood transfusions. Procedure-related adverse events occurred in 60%, and grade 3 or grade 4 post-procedure events were reported in 80%, primarily involving bone marrow suppression and infections associated with neutropenia.
Those figures came from a small group treated over several years at three European centres, so they should not be treated as a forecast of DELUMA’s safety profile. They do, however, show why response data alone will not determine whether the treatment becomes clinically attractive.
Patients enrolled in DELUMA have already received multiple therapies. Participants with hormone receptor-positive disease must generally have progressed on or been unable to tolerate endocrine treatment and a CDK4/6 inhibitor. Patients are also expected to have progressed after an antibody-drug conjugate carrying a topoisomerase-1 inhibitor payload when such treatment is available and appropriate.
This creates a difficult clinical balance. Later-line patients may have limited remaining options and therefore be more willing to consider an intensive organ-directed procedure. At the same time, accumulated treatment exposure may leave them more vulnerable to anaemia, thrombocytopenia, infection and delayed recovery.
Investigators will need to show that patients can recover from HEPZATO and proceed to their assigned chemotherapy without clinically significant disruption. Hospitalisation time, transfusion requirements, treatment delays, early discontinuations and the proportion of patients able to receive both planned procedures will help determine whether the regimen is practical outside a clinical trial.
What would a successful DELUMA study mean for Delcath Systems’ platform strategy?
HEPZATO is already a commercial product rather than a development-stage asset awaiting its first approval. Delcath generated $23.3 million in United States HEPZATO revenue during the first quarter of 2026, compared with $18 million a year earlier. The company reported approximately 36% year-over-year growth in treatment volume and maintained guidance for combined HEPZATO and European CHEMOSAT revenue of at least $100 million for 2026.
The current business remains dependent on metastatic uveal melanoma, a rare cancer in which liver metastases frequently determine prognosis. Expansion into metastatic breast cancer would reduce that indication concentration and provide evidence that the hepatic delivery system can be applied across tumour types when disease becomes liver dominant.
The opportunity is not limited to breast cancer. Delcath is investigating or supporting studies of hepatic perfusion across colorectal cancer, neuroendocrine tumours and other malignancies involving the liver. Positive randomized data in one non-uveal melanoma indication could strengthen the argument that HEPZATO is a platform rather than a single-indication oncology product.
DELUMA is still a Phase 2 study, and dosing the first patient does not reduce the fundamental clinical risk. Delcath previously indicated that primary hepatic progression-free survival results were expected by the end of 2028, with overall survival findings anticipated in 2029. Even a positive study may require further discussions with regulators and potentially additional evidence before a breast cancer label expansion can be pursued.
The programme is also becoming more expensive. Research and development spending increased to $9.8 million in the first quarter of 2026 from $5 million in the corresponding period of 2025, reflecting clinical team expansion and the continuation of multiple Phase 2 trials. Delcath ended March with $89.3 million in cash and investments and no debt, giving it greater capacity to support the programme than many small oncology developers, but clinical expansion will continue competing with commercial investment for capital.
How has Delcath Systems stock responded to the HEPZATO breast cancer milestone?
Delcath Systems shares closed at $13.01 on July 10, 2026, after rising 3.2% on the day the first-patient milestone was announced and falling 3.8% in the following session. The stock was down approximately 1.4% across the five trading sessions ending July 10 but remained about 16.3% above its June 10 closing price.
The shares were also trading close to the upper end of their 52-week range of $8.12 to $13.74. That positioning suggests investors have been responding more broadly to HEPZATO’s commercial growth, expanding treatment-centre network and pipeline optionality rather than treating the first DELUMA dose as a standalone valuation event.
The brief gain followed by a reversal is consistent with the nature of the announcement. First-patient dosing confirms that a trial has moved into execution, but it provides no information about efficacy, safety, enrolment speed or the probability of regulatory success. The programme is therefore better viewed as a long-term expansion opportunity than a near-term clinical catalyst.
Which DELUMA milestones will determine whether HEPZATO can move into breast cancer care?
The next important signal will be enrolment execution. Delcath must activate sites, build referrals and identify eligible patients whose liver disease is sufficiently dominant while their general condition remains strong enough for an intensive procedure.
Treatment delivery will provide another early test. Investigators will be watching how many patients complete the first HEPZATO procedure, how quickly they begin chemotherapy, how many receive the planned second procedure and whether toxicity causes delays or withdrawals.
The eventual hepatic progression-free survival result will show whether direct treatment of the liver changes the trajectory of the disease within that organ. The commercial and regulatory significance of the study, however, will depend on whether that benefit is supported by overall progression-free survival, tumour response, disease control and survival without an unacceptable procedural burden.
DELUMA is consequently a test of more than melphalan activity. It will examine whether a specialised hospital procedure can be integrated into modern metastatic breast cancer treatment after endocrine therapies, targeted drugs and antibody-drug conjugates have been exhausted or are no longer suitable. A convincing result would give Delcath its strongest evidence yet that HEPZATO can develop from a successful rare-cancer product into a broader liver-directed oncology platform.
