Updated investigator results from the Phase II randomized trial of Delcath’s chemosaturation system with melphalan in patients with hepatic metastases from ocular or cutaneous melanoma, presented by James F. Pingpank, MD, FACS, Associate Professor of Surgery at the University of Pittsburgh School of Medicine during the plenary session at the European Multidisciplinary Cancer Congress (EMCC) in Stockholm, shows increased hepatic progression free survival.

Because chemosaturation is intended to be a minimally invasive, repeatable way to deliver high-dose chemotherapy to the liver, the researchers believe it has the potential to complement existing systemic treatments for a patient?s primary disease.

Percutaneous hepatic perfusion
Pingpank is a lead principal investigator of the , will also present the result of a phase III trial (abstract 9304, “Percutaneous Hepatic Perfusion (PHP) vs. Best Alternative Care (BAC) for Patients with Melanoma Liver Metastases – Efficacy Update of the Phase III Trial,”

These updated results include follow-up data from patients through March 2011, an additional 12 months of data maturation from when Dr. Pingpank first presented investigator data from this Phase III trial in June 2010, at the American Society of Clinical Oncology’s Annual Meeting.

Axplora
Port Worthy

High prevalence of Hepatitis B and C
Hepatocellular carcinoma (HCC) is a primary cancer of the liver and one of the most deadly forms of cancer. HCC ranks as the fifth most common solid tumor cancer, with an annual incidence of approximately 20,000 cases per year in the United States, approximately 40,000 cases per year in Europe and approximately 500,000 cases per year worldwide, due to the high prevalence of Hepatitis B and C in developing countries. Usually seen in people aged 50 ? 60, this type of cancer occurs more often in men than women. Treatment options of HCC and prognosis are dependent on many factors including tumor size and location, the underlying functional capacity of the liver, and the stage of the disease. High-grade tumors will have a poor prognosis, while low-grade tumors may go unnoticed for many years. Hepatocellular carcinoma is potentially curable by surgical resection, but surgery is the treatment of choice for only the small fraction of patients with localized disease. The usual outcome is poor, because only 10-20% of HCC can be removed completely using surgery. If the cancer cannot be completely removed, the disease is usually deadly within 6 months.

Advertisement #3

Hepatic progression free survival
The updated investigator-assessed results for the study’s primary endpoint of hepatic progression free survival (“hPFS”) showed that patients in the chemosaturation arm demonstrated median hPFS of 8.0 months compared to 1.6 months in the BAC arm, a significant 6.4 month extension of hPFS (hazard ratio 0.35, p<0.0001). Median overall PFS in the chemosaturation arm was 6.7 months compared to 1.6 months in the BAC arm, an increase of 5.1 months (hazard ratio 0.36, p<0.0001).

Hepatic response rate
As reported previously, the hepatic response rate in the chemosaturation arm was 34% compared to 2% for the BAC arm. In addition, 52% of patients in the chemosaturation arm achieved stable disease, compared with 27% in the BAC group, giving a tumor growth control rate of 86% for the chemosaturation group versus 29% for the BAC group (p<0.001). Patients who crossed from the BAC arm to chemosaturation treatment after progression of liver disease showed consistent efficacy with patients treated on the chemosaturation arm. As expected, there was no difference in overall survival in the randomized study due to the crossover trial design. An analysis of survival trends by patient cohorts indicated that patients treated with chemosaturation, including crossover patients, had a median survival of 11.4 months compared to 4.1 months for BAC patients who did not receive chemosaturation. As of June 30th, 11 patients treated with chemosaturation were still alive compared to two patients in the BAC arm who did not receive chemosaturation.

Extended survival
“The additional 12 months of data and extended survival for a significant percentage of the treated patients confirm our belief that chemosaturation may provide a significantly better option than the few treatments presently available for patients with melanoma metastases in the liver,” said Eamonn P. Hobbs, President and CEO of Delcath. “The hepatic PFS, overall PFS and response rate are consistent with past investigator assessments and highly statistically significant. We are encouraged by the data presented in Stockholm today.”

Other results
Earlier this year, encouraging top-line results were reported from the hepatobiliary cohort of the Phase II clinical trial of the chemosaturation system with melphalan in the treatment of patients with unresectable liver cancer. This study, conducted at the National Cancer Institute (USA), included four patient cohorts including hepatobiliary cancers, and metastatic cancers of neuroendocrine, ocular or cutaneous melanoma, and colorectal (adenocarcinoma) origins.

There were nine patients with tumors of hepatobiliary origin, five hepatocellular carcinomas (HCC) and four cholangiocarcinomas. Both groups had positive efficacy signals. The responses were especially encouraging in the HCC cohort and consisted of confirmed partial response or durable stable disease. The safety profile of the chemosaturation system was consistent with that previously reported for the Company’s Phase III melanoma trial.

“The disease control and anti-tumor activity seen in the HCC arm of this Phase II study is very encouraging for primary liver cancer patients who currently face limited treatment options,” said Eamonn P. Hobbs, President and CEO of Delcath System, Inc. “We believe these results show a strong signal of efficacy, and support our plan to initiate Phase III and Phase IV trials for HCC in the second half of 2012.”

The trial’s primary objectives were to determine the response rate and duration of response to intrahepatic infusion of melphalan with subsequent venous hemofiltration. Secondary objective measures included patterns of recurrence, progression-free survival and overall survival. Additional secondary objectives were to evaluate safety and tolerability in this patient population, and assess filter characteristics including melphalan pharmacokinetics and filtration of cytokines and clotting factors.

Byondis

Advertisement #5