Adding Dendritic Cell-Based Immunotherapy to Chemo Improves OS in Relapsed Ovarian Cancer

The addition of the dendritic cell-based immunotherapy DCVAC/OvCA to standard carboplatin and gemcitabine led to a significant improvement in overall survival (OS) in patients with relapsed, platinum-sensitive, epithelial ovarian cancer, according to final phase II results of the SOV02 trial (NCT02107950) that were presented at the 2019 SGO Annual Meeting.

The DCVAC/OvCA product comprises of active cellular immunotherapy treatments, which are produced and tailored for each patient using their own dendritic cells, in an effort to induce an immune reaction against tumor antigens.

In the phase II study, 71 patients were randomized to receive DCVAC/OvCA in combination with carboplatin/gemcitabine (n = 39) or chemotherapy alone (n = 32). The primary endpoint was progression-free survival (PFS); secondary endpoints were OS, objective response rate, biological progression-free interval, immunological response, and frequency of adverse events (AEs).

At a median follow-up of 36.6 months, there was no significant difference in PFS with the addition of DCVAC/OvCA to chemotherapy at 11.3 months compared with 10.1 months with chemotherapy alone (HR, 0.77; 95% CI, 0.44-1.35; P = .35). However, OS curves demonstrated a favorable increase in the experimental arm versus standard chemotherapy (HR, 0.38; 95% CI, 0.20-0.74; P = .0032); the median OS was 35.5 months in the DCVAC/OvCA arm and 22.1 months in the chemotherapy-alone arm. This led to a 2-year OS rate of 72.4% and 40.9%, respectively (95% CI, 5.3-57.7%).

OncLive: Could you provide the rationale for dendritic cell-based immunotherapy in patients with ovarian cancer? What data exist currently?

In an interview with OncLive, lead study author David Cibula, MD, a gynecologic oncologist at the Gynae Oncology Center of Charles University, highlighted the phase II data on DCVAC/OvCA in combination with chemotherapy for patients with relapsed, platinum-sensitive ovarian cancer, and how it could impact future treatment approaches for this population.Cibula: There is an unmet need to find new treatment modalities [in ovarian cancer]. We also know that due to a relatively high mutational burden, it’s not going to be one simple monotherapy that will work in this population. Therefore, nowadays, we try to combine different types of approaches to treat these patients, and we hope and believe that our approach will be one of them in the future.

Could you provide an overview of the SOV02 trial and discuss the findings being presented at the 2019 SGO Annual Meeting?

Other types of immunotherapy, namely checkpoint inhibitors, have also been explored in combination with other agents in ovarian cancer. What sets DCVAC/OvCA apart?

It’s possible to use this as a single treatment modality, but it’s very unlikely. Currently, we have a standard of care [treatment], and it’s unlikely that any researcher in the future will run a trial without the standard treatment.The phase II trial was an open-label study, and patients were randomized 1:1 to standard-of- care therapy with or without DCVAC/OvCA. This trial showed that this vaccine can significantly improve OS. The hazard ratio was 0.38, which is a very unique figure for this kind of population of patients, with their first recurrence of patients with ovarian cancer who were platinum sensitive, with an at least six-time progression-free interval from the first line of treatment. The difference between the arms in median overall survival was 13.4 months.There are currently many ongoing trials that combine checkpoint inhibitors with the current standard-of-care treatment, including chemotherapy, PARP inhibitors, and bevacizumab (Avastin). However, I like to emphasize that our immunotherapy is very different from checkpoint inhibitors.

What was the safety profile of this combination?

What do you predict will be the next steps in this research?

Could DCVAC/OvCA be explored in combination with other therapies, such as PARP inhibitors?

Are there further subsets of these patients with ovarian cancer who could have the most benefit from this treatment?

The mechanism of action is that it blocks some immunosuppressive mechanism that was built by the cancer. However, the risk is that it can impact the fragile balance in the immune system of the organism, causing some autoimmune problems. With DCVAC/OvCA, these fully maturated dendritic cells stimulate physiological immune reactions against specific cancer antigens, and interestingly they are not associated with any significant morbidity.The safety profile in two phase II trials both found excellent tolerance. There were only AEs related to chemotherapy and none to this vaccine. There were virtually no severe AEs related to this immunotherapy.The next steps will be to conduct a phase III trial, which will be launched in the second half of this year.Definitely. We have to, because this is standard of care. It’s also part of the protocol for our planned phase III trial—that DCVAC/OvCA will be combined with not only chemotherapy but with PARP inhibitors and bevacizumab.Currently, we don’t have any biomarker to predict response to this kind of immunotherapy. We also tried to do a sub-analysis of different subgroups of patients, and we didn’t find any predictive markers but one. It seems from the results —and it’s quite logical for this kind of treatment—that it might work better in patients with a lower tumor burden. Simply, this means that if the tumor is too big, it’s probably too complicated for the immune system to fight with.

Cibula D, Rob L, Mallmann P, et al. Dendritic cell-based immunotherapy (DCVAC/OvCa) with chemotherapy in patients with platinum-sensitive, relapsed, epithelial ovarian carcinoma: aurvival analysis of a phase II, open-label, randomized, multicenter trial (study SOV02). Presented at: 2019 SGO Annual Meeting; March 16-19, 2019; Honolulu, HI. Abstract 35.

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