Rodney P. Rocconi, MD, discusses a subgroup analysis of the phase 2b VITAL study in which the efficacy of maintenance Vigil immunotherapy is explored in patients with newly diagnose advanced ovarian cancer who are homologous recombination proficient.
Rodney P. Rocconi, MD, a gynecologic oncologist, associate director for Clinical Research and professor of Interdisciplinary Clinical Oncology, at USA Health, discusses a subgroup analysis of the phase 2b VITAL study in which the efficacy of maintenance Vigil immunotherapy is explored in patients with newly diagnose advanced ovarian cancer who are homologous recombination proficient.
The subgroup analysis found that with stage III/IV ovarian cancer patients derived clinical benefit from frontline Vigil immunotherapy maintenance, and the treatment was well-tolerated. Benefit was also observed in patients with a BRCA wildtype-positive tumor.
Overall, the subgroup analysis suggests this subgroup of patients is highly sensitive to Vigil therapy, according to Rocconi.
0:08 | We essentially presented updated efficacy results of an ovarian cancer maintenance therapy and frontline of GEM, which is an immune vaccine, and we looked at a subgroup of patients with homologous recombination proficient ovarian cancer. We presented updated data as well as translational evaluation looking for predictive biomarkers of response.
0:38 | So, in the original publication, the primary end point, which was recurrence-free survival in all patients, showed a trend of benefit of recurrence-free survival, but was not statistically significant with a P value of 0.078. As planned in part of this presentation of this abstract, we looked at homologous recombination proficiency, as it appeared to have an enhanced response, as well as being a very tolerable agent.
1:16 | This study is a double-blinded, placebo-controlled randomized phase 2b study of GEM versus placebo in a 1 to 1 fashion. In order to be eligible patients had to have advanced-stage epithelial ovarian cancer either stage III or IV, and have undergone primary therapy of surgery, plus taxane platinum-based chemotherapy and reach a complete clinical response. At that point, patients were then randomized 1 to 1. The vaccine and placebo were given intradermally once a month, from anywhere depending on 4 to 12 cycles, which was determined by the amount of active vaccine that was created. And so again, our primary end point was recurrence-free survival and secondary end points were overall survival in the subgroup analysis based on BRCA mutations as well as homologous recombination status.
2:19 | In this updated data from the as homologous recombination proficient patients, there were 25 patients who received the GEM vaccine and 20 placebo groups were similar across demographic and pathologic variables. This was a well-tolerated agent, where essentially there was no grade 3 or grade 4 adverse events, and the majority of adverse events were mild, with skin irritation at the injection site being the most common adverse event. Also, those were equal between the placebo in GEM groups.
2:54 | From an efficacy standpoint and homologous recombination proficiency, we saw very encouraging results with the statistical improvement in both recurrence-free survival benefit from 5.7 up to 10.6 months, that correlated to a 61% reduction of recurrence, as well as an improvement in the overall survival benefit from 26.9 months in placebo to median not reached in the GEM arm, and that was a 66% reduction in death.
3:25 | Looking at our long-term data, which a median of 58 months of follow up, which was analyzed up until April of 2021, that overall survival benefit was maintained. Two-year overall survival was 92% in the GEM arms compared to 55 in placebo, and in 3-year overall survival was 70% in the GEM compared to 40% in the placebo arm. Both of those were statistically significant. I did mention some of the translational end points. We looked at gene-protein and protein-protein interactions using a large database [the String database. And by analyzing that, based on the computational analysis of related proteins, looking for kind of a molecular subgroup of patients to predict the best response, the homologous recombination proficient set of proteins with p53 set of proteins gave the most favorable outcomes, where the recurrence-free survival was 5.6 in the placebo compared to 21 months in the GEM group. And the overall survival again, was maintained with a significant benefit in that subgroup analysis as well. So, it was very promising not only from our extended follow up with immediate follow up again of 58 months, but in our translational end points as well as we try to home in on predictive biomarkers that could be of use in the future.