Celsion Announces Final Clinical and Translational Research Data from its OVATION Study at the AACR Special Conference on Ovarian Cancer
100% Disease Control; 86% Objective Response Rate and 86% R0 & R1 Surgical Resection Rate in All Patients Treated in Four Dose-Escalating Cohorts
Clear Evidence of Biological Activity Including Dose Dependent Increases in Inflammatory Cytokines (IL-12 and IFN-g), Decreases in VEGF Levels and No Dose Limiting Toxicities
Expert Advisory Board Endorses Randomized Phase II in Newly Diagnosed Stage III and IV Ovarian Cancer
The Company updated the translational data from the OVATION Study in a poster presentation at the
The Company also held an Advisory Board Meeting on
Translational Research Data
Key translational research findings from all evaluable patients are 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.
- Analysis of peritoneal fluid by cell sorting, not reported before, shows treatment-related decrease in the percentage of immunosuppressive T-cell (Foxp3+), which is consistent with the reduction of Foxp3+ T-cells in the primary tumor tissue, and a shift in tumor naïve CD8+ cell population to more efficient tumor killing memory effector CD8+ cells.
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.
"These distinct immunological changes in the local disease environment are likely to translate into clinical benefit and warrant the continued development of our GEN-1 IL-12 immunotherapy as a potential adjuvant, in both first and second-line ovarian cancer," said Dr. Kunle Odunsi, Deputy Director, Chair of Gynecologic Oncology and
- 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.
- Of the eight patients who have received GEN-1 treatment over one year ago (cohort 1 - 3) and are being followed; only two patients' cancer has progressed. This compares favorably to the historical median progression free survival (PFS) of 12 months for newly-diagnosed patients with Stage III and IV ovarian cancer that undergo neoadjuvant chemotherapy followed by interval debulking surgery. Of the remaining six patients who have been on the study for over one year, their average PFS as of
September 30, 2017is 18 months with the longest progression-free patient at 24 months.
"We have completed enrollment of our Phase Ib OVATION Study in newly diagnosed ovarian cancer patients to determine GEN-1's clinical and biological activity in combination with standard chemotherapy. The remarkable surgical outcomes for all patients completing the prescribed eight weekly treatments of GEN-1 reinforce our belief in the promise of GEN-1's ability to work safely and effectively in advanced ovarian cancer," said Dr.
The poster presentation will be available on Celsion's website under "News & Investors - Scientific Presentations."
OVATION Study Design
The Phase Ib trial was designed to evaluate weekly intraperitoneal dosing of GEN-1 in combination with neoadjuvant chemotherapy, the standard of care for patients newly diagnosed with ovarian cancer. Concurrently with neoadjuvant chemotherapy, enrolled patients will receive escalating weekly doses of GEN-1, from levels beginning at 36mg/m², to 47mg/m², 61mg/m² and 79mg/m² weekly for 8 treatments in total, with interval debulking surgery to follow. The regimen will primarily be evaluated for its safety and tolerability.
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