Delcath Systems has achieved a significant milestone in expanding the therapeutic applications of its liver-directed treatment platform, dosing the first patient in a Phase 2 clinical trial evaluating HEPZATO in combination with standard of care treatment for liver-dominant metastatic colorectal cancer (mCRC). The trial launched at the City of Hope National Medical Center, marking the company's entry into a new indication beyond its approved use in metastatic uveal melanoma.
Trial Design and Patient Population
The randomized, controlled Phase 2 trial will evaluate the safety and efficacy of HEPZATO in combination with trifluridine-tipiracil and bevacizumab compared to trifluridine-tipiracil and bevacizumab alone in patients with liver-dominant mCRC receiving third-line treatment. Approximately 90 patients will be enrolled across more than 20 sites in the United States and Europe.
The study targets patients who present with significant liver disease burden, determined through radiological and clinical criteria. This patient population represents an area of significant unmet medical need, with limited therapeutic alternatives available for third-line treatment.
Market Opportunity and Timeline
Delcath estimates the total addressable market for liver-dominant mCRC receiving third-line treatment ranges between 6,000 and 10,000 patients annually in the United States. The company aims to provide a novel treatment option for this underserved patient population.
Results from the trial's primary endpoint, hepatic progression-free survival (hPFS), are anticipated by mid-2028, while overall survival (OS), a secondary endpoint, is expected in late 2028.
HEPZATO Technology Platform
HEPZATO KIT is comprised of the chemotherapeutic drug melphalan and Delcath's proprietary Hepatic Delivery System (HDS). The HDS isolates hepatic venous blood from systemic circulation while simultaneously filtrating hepatic venous blood during melphalan infusion and washout. This approach enables loco-regional delivery of relatively high melphalan doses, potentially inducing clinically meaningful tumor responses with minimal hepatotoxicity and reduced systemic exposure.
In the United States, HEPZATO KIT is approved as a liver-directed treatment for adult patients with metastatic 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.
Clinical Significance
"This milestone marks a significant advancement in our mission to address unmet needs in liver-dominant cancers," said Vojislav Vukovic, Chief Medical Officer of Delcath Systems. "Dosing the first patient in this Phase 2 trial is an exciting step toward exploring HEPZATO's potential to provide a new treatment option for patients with metastatic colorectal cancer, building on its proven role in metastatic uveal melanoma."
The trial represents Delcath's strategy to expand the clinical utility of its liver-directed treatment platform beyond uveal melanoma into other liver-dominant malignancies, potentially addressing a significantly larger patient population with limited treatment options in the third-line setting.
