ThermoDox® — Pipeline within a Program
The HEAT Study – Primary Liver Cancer
(Hepatocellular Carcinoma Study of RFA and ThermoDox)
The HEAT Study is a pivotal, 700-patient, double-blind, placebo-controlled, international Phase III study designed to evaluate the safety and efficacy of ThermoDox® in combination with radiofrequency ablation (RFA) in patients with non-resectable hepatocellular carcinoma (HCC or primary liver cancer). The trial is being conducted at 79 clinical sites in the United States, Canada, Italy, China, Taiwan, Hong Kong, Korea, Thailand, Malaysia and the Philippines. The primary endpoint for the study is progression free survival (PFS), with a secondary confirmatory endpoint of overall survival (OS). A total of 380 events of progression are required to reach the planned final analysis of the study, which is expected to occur in late 2012 or early 2013.
As the largest trial ever conducted in intermediate HCC, the HEAT Study has been designed to support registration filings in multiple regions worldwide, including the U.S., countries is the Asia Pacific region and Europe. In the U.S., the trial is being conducted under a Special Protocol Assessment with the FDA, and Celsion has received both Fast Track and Priority Review designations and reached a 505b(2) agreement with the FDA, establishing the potential for an accelerated U.S. regulatory review process. ThermoDox® has also received Orphan Drug designations for HCC in both the U.S. and Europe, which provide for 7 and 10 years, respectively, of marketing exclusivity. In recognition of the desperate need for new treatment options in primary liver cancer, the National Cancer Institute has recognized the HEAT Study as a “Priority Clinical Trial”.
The DIGNITY Study – Breast Cancer
The DIGNITY Study is a multicenter, single-arm open label, dose-escalating Phase I/Phase II trial of ThermoDox® plus hyperthermia in up to 109 patients with recurrent chest wall (RCW) breast cancer. The trial is designed to establish a safe therapeutic dose in Phase I, and then advance into a Phase II study to evaluate safety and evidence of clinical activity, with a primary endpoint of durable complete local response. Celsion has completed enrollment of the Phase I portion of the study and selected a dose for use in a Phase II trial. The Phase II portion of the DIGNITY Study protocol has been reviewed by the FDA, and Celsion intends to commence the Phase II study in 2012. The FDA has indicated that the trial may be considered pivotal, pending a review of the data supporting the endpoint.
The DIGNITY Study builds upon promising data from a Phase I dose escalation study conducted at the Duke University Medical Center, in which 16 RCW breast cancer patients treated with ThermoDox® demonstrated evidence of either stable disease, partial response or complete response. Toxicities are consistent with doxorubicin, the active agent in ThermoDox® and a widely used chemotherapeutic with a well established safety profile.
The ABLATE Study — Colorectal Liver Metastases
In 2011, Celsion initiated a Phase II study of ThermoDox® in combination with RFA for the treatment of colorectal liver metastases (The ABLATE Study). The trial is expected to enroll up to 88 patients with colorectal cancer metastasized to the liver. Patients will be randomized to receive either RFA plus ThermoDox® or RFA alone for the treatment of liver tumors. The primary study endpoint is based on one year local tumor recurrence, with secondary endpoints of time to progression and overall survival.
ThermoDox Plus HIFU
Celsion is exploring ThermoDox in combination with high frequency ultrasound (HIFU) as a non-invasive treatment for a variety of cancers. The Company has established a joint research collaboration with Phillips Healthcare to evaluate ThermoDox plus HIFU in a clinical study in bone metastases, with pain palliation as the primary endpoint, and with the Focused Ultrasound Foundation, the Company is supporting preclinical studies exploring the use of ThermoDox® plus HIFU for the treatment of pancreatic cancer. Most recently, Celsion announced a collaboration with the University of Oxford to begin a clinical study of ThermoDox® plus HIFU to treat metastatic liver cancer.
Additional Development Opportunities
In addition to the current development programs, Celsion is considering additional expansion opportunities for its ThermoDox® pipeline, including other tumor indications for which doxorubicin is currently approved.