ThermoDox® — Pipeline within a Program

THE OPTIMA STUDY – PRIMARY LIVER CANCER

The Phase III OPTIMA study is designed to evaluate ThermoDox® in combination with standardized radiofrequency ablation (sRFA 45) in patients with primary liver cancer (hepatocellular carcinoma, or HCC). The study is currently enrolling, and will include approximately 550 patients at up to 100 sites in North America, Europe, China, and the Asia-Pacific region.

The two-arm, double-blinded, randomized study will compare ThermoDox plus sRFA 45 to sRFA 45 alone; sRFA will be administered for a minimum of 45 minutes in both arms. In the ThermoDox + sRFA 45 arm, the ≥ 45-minute sRFA treatment time allows for increased local ThermoDox perfusion and ultimately, a high tissue concentration of doxorubicin and improved patient outcomes. The primary endpoint is overall survival (OS); secondary endpoints include progression-free survival (PFS) and safety.

The OPTIMA study is powered to demonstrate a 33% improvement in OS. Its design is supported by an exhaustive retrospective analysis of a large subgroup of 285 patients in a Phase III trial in primary liver cancer, is based on convincing post-hoc OS data, and is further reinforced by prospective confirmatory preclinical data in computational models. In a subgroup of 285 HEAT study participants, we noted a 57% improvement in OS in the ThermoDox + sRFA 45 arm, compared to those who received sRFA 45 alone; these findings have remained constant over six quarterly data sweeps (p = 0.037). Supported by key opinion leaders in HCC clinical research, our post-hoc analysis suggests that a 33% improvement in OS is an attainable target for the OPTIMA study.

THE DIGNITY STUDY – RECURRENT CHEST WALL (RCW) BREAST CANCER

Celsion is currently enrolling patients in the Phase II DIGNITY study, which is evaluating ThermoDox plus local hyperthermia in patients with recurrent chest wall (RCW) breast cancer, a subtype of breast cancer that is particularly difficult to treat. Patients are eligible if they have failed to respond to at least two lines of chemotherapy following mastectomy, and have failed to respond to radiation. The open-label study is being conducted at five sites in the U.S.

Interim findings show impressive clinical activity, with a local response rate of 50%, including three complete responses and two partial responses. Additionally, 60% of DIGNITY study participants have experienced disease stabilization. Those findings are consistent with the local response rate of 48.3% observed in 24 patients enrolled in two previous Phase I studies in RCW breast cancer.

THERMODOX PLUS HIFU

Celsion is evaluating ThermoDox in combination with MRI-guided high-frequency ultrasound (HIFU) as a non-invasive treatment for a variety of cancers. The most advanced of these initiatives, conducted in partnership with Oxford University in the U.K., is recruiting patients for a Phase II trial of ThermoDox plus HIFU in metastatic liver cancer. We are also partnering with the University of Utrecht, The Netherlands and the Center for Translational Molecular Medicine (CTMM) on a Phase II trial of ThermoDox plus HIFU in patients with breast cancer; this trial, which is currently enrolling, is supported through a $10 million European Cooperative Grant. Additionally, we are collaborating with the University of Washington and the Focused Ultrasound Foundation on a pre-clinical study of ThermoDox plus HIFU for the treatment of pancreatic cancer, and with Brigham & Women’s Hospital and Harvard Medical School on a pre-clinical study of this combination in glioblastoma multiforme (GBM), a type of brain cancer. The GBM study is supported by a $1 million grant from the National Institutes of Health (NIH).