Delcath Systems, Inc. (NASDAQ: DCTH) announced today that the U.S. Food and Drug Administration (FDA) has completed its 30-day review of the company's Investigational New Drug (IND) application, clearing the path for a Phase 2 clinical trial of HEPZATO™ in patients with liver-dominant metastatic breast cancer (mBC). This regulatory milestone allows Delcath to begin patient enrollment in the United States.
The Phase 2 trial will evaluate HEPZATO in combination with standard of care (SOC) versus SOC alone in patients with liver-dominant HER2-negative metastatic breast cancer who have experienced failure of previous treatments. Physicians will have the choice of eribulin, vinorelbine, or capecitabine as the standard of care component.
Trial Design and Timeline
The randomized, controlled trial will enroll approximately 90 patients across more than 20 clinical sites throughout the United States and Europe. Patient enrollment is expected to begin in the fourth quarter of 2025.
The study's primary endpoint is hepatic progression-free survival, with results anticipated by the end of 2028. Data on overall survival, a secondary endpoint, is expected in 2029.
Gerard Michel, Chief Executive Officer of Delcath Systems, emphasized the significance of this development: "This randomized Phase 2 trial marks an important milestone as we expand the clinical investigation of HEPZATO into patients with liver-dominant metastatic breast cancer. We are excited to bring new hope to patient populations in indications beyond metastatic uveal melanoma and to further demonstrate the potential of HEPZATO to address unmet needs in oncology."
Addressing a Critical Unmet Need
According to Delcath's management, approximately 7,000 patients in the United States annually are affected by HER2-negative metastatic breast cancer with liver metastases who could be candidates for third-line treatment. This population includes patients with a significant burden of liver metastases, which are often the primary cause of mortality.
By focusing on this specific demographic, Delcath aims to provide a novel therapeutic option for patients with limited treatment alternatives. The liver-directed approach could potentially offer improved outcomes for patients whose disease has progressed despite multiple prior lines of therapy.
HEPZATO Technology
HEPZATO KIT (HEPZATO (melphalan) for Injection/Hepatic Delivery System) is Delcath's proprietary product designed to deliver high-dose chemotherapy directly to the liver while controlling systemic exposure and associated side effects during a percutaneous hepatic perfusion (PHP) procedure.
The system comprises the chemotherapeutic drug melphalan and Delcath's proprietary Hepatic Delivery System (HDS), which isolates hepatic venous blood from systemic circulation while simultaneously filtering the blood during melphalan infusion and washout. This approach enables loco-regional delivery of a relatively high melphalan dose, potentially inducing meaningful tumor response with minimal hepatotoxicity and reduced systemic exposure.
HEPZATO KIT is currently approved in the United States as a liver-directed treatment for adult patients with metastatic uveal melanoma (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.
Expanding Treatment Applications
This new clinical trial represents a significant expansion of HEPZATO's potential applications beyond its current indication for metastatic uveal melanoma. Michel noted that the study "underscores our commitment to broadening the applications of HEPZATO and the underlying hepatic delivery system, positioning us as a platform technology that can offer directed treatment options for a variety of liver-dominant cancers."
The expansion into metastatic breast cancer could potentially open the door for investigating HEPZATO in other cancer types with liver metastases, addressing a broader range of patients with limited therapeutic options.
In Europe, the device-only configuration of the HDS is regulated as a Class III medical device and is approved for sale under the trade name CHEMOSAT Hepatic Delivery System for Melphalan, where it has been used to treat various liver cancers at major medical centers.
As the trial progresses, oncologists and patients will be watching closely to see if this innovative approach can provide meaningful benefits in the challenging setting of liver-dominant metastatic breast cancer, where new therapeutic options are urgently needed.
