Combining the DNA-based immunotherapy GEN-1 with neoadjuvant standard-of-care chemotherapy to treat newly-diagnosed advanced ovarian cancer patients who will undergo interval debulking surgery seems to be a promising therapeutic approach, according to data from the OVATION study. Data recently announced by Celsion Corporation showed promising efficacy signals in the first nine patients dosed, including 100% disease control rate, with no dose-limiting toxicities.
“While the patient number in this trial may be small, the consistency and robust nature of the data across all three cohorts and the encouraging clinical responses underscore the potential of GEN-1 to serve as an effective, safe IL-12 immunotherapy in ovarian cancer,” Nicholas Borys, MD, Celsion’s chief medical officer, said in a press release. “I am particularly impressed with the pathological response data, which is known to be associated with prolonged survival in this patient population. The data generated support continued evaluation of GEN-1 in ovarian cancer, and we look forward to seeing how GEN-1 performs in the fourth and final study cohort.”
Celsion’s GEN-1 is an IL-12 DNA vector encapsulated by lipid molecules that target tumor cells, allowing for a targeted delivery of IL-12 to the tumor site, and consequent reduction in serious toxicities.
The OVATION study (NCT02480374) is a Phase 1b dose-escalating trial meant to assess the safety and efficacy of GEN-1 in newly diagnosed ovarian cancer patients. It was designed to enroll three to six patients per dose cohort, to identify a tolerable dose with maximized immune responses.
The first three cohorts enrolled three patients each, and results showed a complete response (CR), five partial responses (PR), and three stable disease (SD) in the first nine patients dosed. This accounted for a 100% disease control rate and a 66% objective response rate.
Among these nine patients, eight had successful resections of their tumors, the majority of which no residual disease or microscopic residual disease after surgery. One patient was ineligible for surgery due to a medical complication not related to the treatment.
Importantly, of the eight patients who underwent surgery, one had a complete pathological response (cPR), three had a micro-pathological response, and four had a macro-pathological response. These results show improvements to historical data, which show that fewer than 7% of patients reach a cPR, which is associated with a median overall survival of 72 months (more than three years longer than those who do not reach cPR).
Celsion also reported immunological data from the first two cohorts of the OVATION study. Results showed that in the four patients available for analysis, the ratio of tumor-killing versus suppressive immune cells was increased at the time of surgery, compared to samples collected before the start of GEN-1 treatment. The remaining two patients were not assessed because in one of them there was a cPR, and thus no tumor available for analysis, and the other did not undergo surgery.
Celsion is now enrolling patients for the fourth OVARIAN cohort, and expects to report the final data from the study in early 2017. Future GEN-1 studies will include a Phase 1/2 clinical trial assessing this agent in combination with Avastin (bavecizumab) and Doxil (doxorubicin).
“The clinical and translational data generated to date are meaningful and reinforce our confidence in the potential of GEN-1 to address advanced Stage III and IV ovarian cancer, a population clearly in need of effective therapies,” said Khursheed Anwer, PhD, Celsion’s chief scientific officer. “We anticipate completion of enrollment in the fourth patient cohort in the coming weeks, and will continue to assess a potential accelerated clinical development path for GEN-1. In parallel, we are currently evaluating translational data from the study, which we expect to report before the end of the fourth quarter,” said Anwer.