Phase II Trial Launches to Evaluate Hepzato in Liver-Dominant Colorectal Cancer

Delcath Systems has announced that the first patient has been dosed in its Phase II clinical trial at the City of Hope National Medical Center. The global study is assessing Hepzato (melphalan/Hepatic Delivery System) in combination with standard of care treatment for liver-dominant metastatic colorectal cancer (mCRC).¹

In a press release, Vojislav Vukovic, chief medical officer of Delcath, said: “This milestone marks a significant advancement in our mission to address unmet needs in liver-dominant cancers. Dosing the first patient in this Phase II 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.”

Study design and endpoints

This randomized, controlled Phase II study is evaluating the safety and efficacy of Hepzato along with trifluridine-tipiracil and bevacizumab compared to trifluridine-tipiracil and bevacizumab alone in patients with liver-dominant mCRC receiving third-line treatment.

• The trial will enroll approximately 90 patients across more than 20 sites in the United States and Europe.
• The primary endpoint is hepatic progression-free survival, with results expected by mid-2028.
• A key secondary endpoint is overall survival, with results anticipated in late 2028.

Previous FDA approval in uveal melanoma

Hepzato, a combination drug and device product, was approved by the FDA in August 2023 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.²

The approval was based on positive results from the single arm, multicenter, open label, Phase III FOCUS trial (NCT02678572). Results from the study showed:

• The overall response rate was 36.3% (95% CI: 26.4–47.0).
• Median duration of response was 14 months (95% CI: 8.3–17.7).
• The disease control rate was 73.6% (95% CI: 63.3–82.3).
• Responses included seven complete responses (7.7%) and 26 partial responses (28.6%).

In a press release from the time, Gerard Michel, chief executive officer of Delcath, said: "FDA approval of Hepzato Kit marks the beginning of a new chapter for Delcath and the culmination of the Company's commitment to bring this treatment option to patients suffering from metastatic uveal melanoma. We look forward to partnering with cancer centers across the country to build a network of treatment sites trained in the use of this novel therapy."

Vukovic added: "Hepzato Kit is the only liver-directed therapy that can treat the whole liver. Scientific literature supports that Hepzato Kit may have broad applicability in other tumor types, and we intend to expand our development efforts beyond uveal melanoma given the high incidence of unresectable hepatic dominant tumors."

Phases of the FOCUS study

The FOCUS study included three phases: screening, treatment, and follow-up.³

• In the screening phase (within 28 days before eligibility), patients underwent assessments for medical history, physical exam, Eastern Cooperative Oncology Group (ECOG) status, electrocardiogram (ECG), echocardiogram (ECHO) labs, quality of life questionnaire, imaging, and medication review. Angiograms were performed for reported prior liver or vascular surgery.
• In the treatment phase, eligible patients received up to six melphalan/Hepatic Delivery System cycles (3.0 mg/kg IBW), each 6 weeks, with up to a 2-week delay if needed. Tumor response was assessed every 12 weeks until progression or treatment discontinuation. Maximum treatment duration was 12 months.
• In the follow-up phase, patients underwent imaging every 12 weeks until progression, then survival follow-up by phone every 3 months. Monitoring included risks of myelodysplasia and secondary leukemia.

References

1. Delcath Systems Announces First Patient Dosed in Phase 2 Clinical Trial of HEPZATO™ in Liver-Dominant Metastatic Colorectal Cancer. News release. Delcath Systems. August 19, 2025. Accessed August 19, 2025. https://www.businesswire.com/news/home/20250819643252/en/Delcath-Systems-Announces-First-Patient-Dosed-in-Phase-2-Clinical-Trial-of-HEPZATO-in-Liver-Dominant-Metastatic-Colorectal-Cancer

2. Delcath Systems, Inc. Announces FDA Approval of HEPZATO KIT™ for the Treatment of Adult Patients with Unresectable Hepatic-Dominant Metastatic Uveal Melanoma. News release. August 14, 2023. Accessed August 19, 2025. https://delcathsystemsinc.gcs-web.com/news-releases/news-release-details/delcath-systems-inc-announces-fda-approval-hepzato-kittm

3. Percutaneous Hepatic Perfusion in Patients With Hepatic-dominant Ocular Melanoma (FOCUS). ClinicalTrials.gov. Updated December 21, 2023. Accessed August 19, 2025. https://clinicaltrials.gov/study/NCT02678572