Celsion Corporation Provides Corporate Update and 2018 Outlook
Company Advances ThermoDox® for Treatment of Primary Liver Cancer Following Independent Data Monitoring Committee's Unanimous Recommendation to Continue Phase III OPTIMA Study
OPTIMA Study Enrollment Reached 74% Enrollment at Year-End, With Enrollment Completion Expected in Third Quarter 2018
Initiation of Enrollment of Phase I Portion of OVATION II Study of GEN-1 for Treatment of Ovarian Cancer Anticipated in the First Half of 2018
Cash Position of
OPTIMA Study Update. The Company announced that, as of year-end 2017, enrollment in the OPTIMA Study reached 74% of the 550 patients necessary to ensure that its primary endpoint, overall survival, can be evaluated with statistical significance. The OPTIMA Study is currently enrolling at 69 sites in
HEAT Study Data Support the Phase III OPTIMA Study. A manuscript titled "Phase III HEAT Study Adding Lyso-Thermosensitive Liposomal Doxorubicin to Radiofrequency Ablation in Patients with Unresectable Hepatocellular Carcinoma Lesions," was published in the high impact, peer-reviewed medical journal,
- The final overall survival (OS) analysis from the HEAT study demonstrated that in a large, well-bounded subgroup of patients (n=285 patients, 41% of the previous 701 patient HEAT Study), treatment with a combination of ThermoDox® and standardized RFA provided an average 58% improvement in OS compared to standardized RFA alone. The Hazard Ratio (HR) was 0.63 (95% CI 0.43 - 0.93) with a p-value of 0.0198. In this large subgroup, median OS for the ThermoDox® plus standardized RFA group translated into a 25.4-month (more than 2.1 years) survival benefit over the standardized RFA-only group, totaling approximately 80 months (6-1/2 years, which is considered a curative treatment for HCC) for the ThermoDox® plus standardized RFA group, versus 53 months for the standardized RFA-only group.
Conclusions from the publication were further supported by results from a 2016 independent retrospective analysis of the HEAT Study conducted by the
R&D Day. Lead investigators (
OVATION Study Update. In
The Company further reported encouraging clinical data from the first fourteen patients who completed treatment in the OVATION Study. GEN-1 plus standard chemotherapy produced positive clinical results, with no dose-limiting toxicities and promising dose-dependent efficacy signals, which correlate well with successful surgical outcomes as summarized below:
- Of the fourteen patients treated in the entire study, two (2) patients demonstrated a complete response, ten (10) patients demonstrated a partial response and two (2) patients demonstrated stable disease, as measured by RECIST criteria. This translates to a 100% disease control rate ("DCR") and an 86% objective response rate ("ORR"). Of the five patients treated in the highest dose cohort, there was a 100% objective response rate with one (1) complete response and four (4) partial responses.
- Fourteen patients had successful resections of their tumors, with nine (9) patients (64%) having an R0 resection, which indicates a microscopically margin-negative resection in which no gross or microscopic tumor remains in the tumor bed. Seven out of eight (87%) patients in the highest two dose cohorts experienced a R0 surgical resection. All five patients treated at the highest dose cohort experienced a R0 surgical resection.
- All patients experienced a clinically significant decrease in their CA-125 protein levels as of their most recent study visit. CA-125 is used to monitor certain cancers during and after treatment. CA-125 is present in greater concentrations in ovarian cancer cells than in other cells.
Key translational research findings from all evaluable patients in the study were consistent with the earlier reports from partial analysis of the data and are summarized below:
- The intraperitoneal treatment of GEN-1 in conjunction with neoadjuvant chemotherapy resulted in dose-dependent increases in IL-12 and Interferon-gamma (IFN-g) levels that were predominantly in the peritoneal fluid compartment with little to no changes observed in the patients' systemic circulation. These and other post-treatment changes including decreases in VEGF levels in peritoneal fluid are consistent with an IL-12 based immune mechanism.
- Consistent with the previous partial reports, the effects observed in the IHC analysis were pronounced decreases in the density of immunosuppressive T-cell signals (Foxp3, PD-1, PDL-1, IDO-1) and increases in CD8+ cells in the tumor microenvironment.
- The ratio of CD8+ cells to immunosuppressive cells was increased in approximately 75% of patients, suggesting an overall shift in the tumor microenvironment from immunosuppressive to pro-immune stimulatory following treatment with GEN-1. An increase in CD8+ to immunosuppressive T-cell populations is a leading indicator and believed to be a good predictor of improved overall survival.
- These translational research findings demonstrate that GEN-1 in ovarian cancer patients is biologically active and creates a shift in the primary tumor and in the surrounding tumor environment in the peritoneal cavity that promotes a pro-immune T-cell population dynamic and conversion of tumor naïve T-cell into cytotoxic effector T-cells in the tumor microenvironment.
Progression-Free Survival for Patients Treated per Protocol in the Phase IB OVATION Study Continues to be Followed. Of the thirteen patients who received GEN-1 treatment in all four dose-escalating cohorts, only four patients' cancer have
progressed as of
- Cohort 1 (36 mg/m²) - All patients have progressed; Average PFS was 19.25 months; Longest progression-free patient in 1st cohort was 24.8 months.
- Cohort 2 (47 mg/m²) - No patients have progressed after 21 months.
- Cohort 3 (61 mg/m²) - One patient has progressed after 14 months; Two other patients in 3rd cohort are progression free over 18 months
- Cohort 4 (79 mg/m²) - No patients have progressed; Average PFS for these five patients in 4th cohort is 15 months.
Advisory Board Recommendation and FDA Submission Enable OVATION II Study Enrollment Initiation, Expected in First Half of 2018. The Company held an Advisory Board Meeting on
The Phase I/II trial was developed with extensive input from the Company's
The OVATION II Study is designed with a single dose escalation phase to 100 mg/m², followed by a continuation at the selected dose in Phase II in an open label, 1:1
randomized design up to 90 patients with Stage III/IV ovarian cancer at up to fifteen
Financial Guidance/Unaudited Cash and Investments
- Complete enrollment of Phase III pivotal
OPTIMA Study for primary liver cancer
- First pre-planned efficacy analysis in first half of 2019
- Second pre-planned efficacy analysis expected in the second half of 2019
- Initiate Phase I portion of OVATION II Study in the first half of 2018
- Data from Phase I portion of trial in second half of 2018
- Data from Phase I portion of trial in second half of 2018
- Initiate Phase II randomized portion of OVATION II Study in second half of 2018
- Data from Phase II randomized portion of OVATION II Study to be reported throughout 2019 (Open Label Design)
About the OPTIMA Study
The Phase III OPTIMA Study is
expected to enroll up to 550 patients in up to 75 clinical sites in
About GEN-1 Immunotherapy
GEN-1, designed using
About Celsion Corporation
For more information on
ThermoDox is a registered trademark of
Celsion Investor Contact
Jeffrey W. ChurchSr. Vice President and CFO 609-482-2455 email@example.com
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