Celsion Announces GEN-1 Data Presentation at ASCO-SITC Clinical Immuno-Oncology Symposium
100% Objective Response Rates and 88% Complete (R0) Resection Rates in Highest Dose Cohorts
GEN-1 Intraperitoneally Delivered Durable Local Levels of Pro-Immune IL-12 and Related Cytokines
Dose Dependent Reduction in Immunosuppressive Biomarkers Suggest Positive Effect on Tumor Microenvironment
“In this Phase IB dose-escalation study, the 14 patients who were evaluable for response, 100% of patients administered NAC plus the two higher doses of GEN-1 experienced an objective tumor response (defined as a partial or complete response) compared to only 60% of patients given the two lower doses,” said Dr. Thaker. “Patients in the higher dose cohorts also had a high surgery success rate, with 88% of these patients achieving the optimal outcome of a complete (R0) resection. Pre- and post-treatment levels of key ovarian cancer biomarkers were also measured as part of this study and showed marked reduction in immunosuppressive response across multiple biomarkers post-treatment, including FOXP3 and IDO-1 – an outcome not previously observed with NAC treatment alone. Together, these findings indicate that GEN-1 may alter the tumor microenvironment and may improve ovarian cancer outcomes in combination with NAC. As a clinician, these observations are very encouraging, and I look forward to further data from the GEN-1 development program to more fully characterize GEN-1’s potential to treat patients with this deadly disease.”
“The OVATION I Study has provided important data that not only suggest GEN-1’s ability to safely be administered with standard NAC but also indicate its potential to meaningfully influence progression-free survival (PFS), which for patients treated per protocol in this study demonstrated a median PFS of 21 months, a favorable result relative to the PFS historical average of 12 months for women with ovarian cancer,” said
The Phase IB OVATION 1 Study, which evaluated escalating doses of GEN-1 (36 mg/m2, 47 mg/m2, 61 mg/m2 and 79 mg/m2) administered intraperitoneally in combination with three cycles of neoadjuvant chemotherapy prior to interval debulking surgery, followed by three cycles of NAC in the treatment of newly diagnosed patients with Stage III/IV ovarian cancer, demonstrated median PFS of 21 months in patients treated per protocol (n=13) and 17.1 months for the intent-to-treat population (n=18) for all dose cohorts, including three patients who dropped out of the study after 13 days or less, and two patients who did not receive full NAC and GEN-1 cycles.
Pathological changes were assessed as part of the study, with the density of markers measured in tissue sections assessed via immunohistochemistry staining. Among patients administered the high doses of GEN-1 (n=8), pre-treatment to post-treatment reductions in key biomarkers were observed (FoxP3 -62.5%; IDO-1 -60%; PD-1 -62.5%; PD-L1 -37.5%). Reductions were also observed in patients administered the lower doses of GEN-1 (n=4) for all but one of the four key biomarkers (FoxP3 -40%; IDO-1 -40%; PD-1 +25%; PD-L1 -37.5%). The ratio of CD8+ cells to the four key immunosuppressive cell signals increased following treatment in 60 - 80% of patients.
Dose-limiting toxicity was not reached in the OVATION I Study. The most common adverse events attributed to GEN-1 in the OVATION I Study were nausea, abdominal pain/cramping, fatigue, vomiting, diarrhea and neutropenia.
The presentation titled, “Phase I study of the safety and activity of formulated IL-12 plasmid administered intraperitoneally in combination with neoadjuvant chemotherapy in patients with newly diagnosed advanced stage ovarian cancer” was presented as part of Oral Abstract Session C on
GEN-1, designed using
The OVATION 2 Phase I/II study in patients newly diagnosed with Stage III/IV ovarian cancer, was initiated in
ThermoDox® is a registered trademark of
Source: Celsion CORP