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Dendritic cell-based immunotherapy enters phase 3 development for ovarian cancer
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Researchers are preparing to launch a phase 3 trial evaluating a dendritic cell-based immunotherapy known as DCVAC after phase 2 data showed the addition of DCVAC to chemotherapy significantly improved OS among women with ovarian carcinoma.
The trial, which was presented at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer, included women with platinum-sensitive, relapsed epithelial ovarian cancer.
DCVAC (Sotio) is a novel autologous immunotherapy developed from patients’ white blood cells. In addition to ovarian cancer, the product is also being tested as a treatment for prostate cancer and non-small cell lung cancer, according to the manufacturer.
For the phase 2 SOV02 trial, David Cibula, MD, PhD, chair of the Gynecologic Oncology Center at General University Hospital of Charles University in Prague, and colleagues randomly assigned 64 patients with serous, endometrioid or mucinous ovarian carcinoma to carboplatin and gemcitabine for six to 10 cycles (n = 32) or to the chemotherapy regimen plus five induction doses of DCVAC every 3 weeks starting with the second chemotherapy cycle, followed by five maintenance doses every 6 weeks thereafter.
Although there was no significant difference in the primary endpoint of PFS, the addition of DCVAC was associated with substantially higher 2-year survival rates (72.4% vs. 40.9%) and median OS (35.5 vs. 22.1 months) compared with chemotherapy alone.
Previously, results of another phase 2 trial, SOV01, showed that DCVAC improved PFS when administered sequentially after chemotherapy among women with epithelial ovarian carcinoma.
A larger, phase 3 trial assessing DCVAC in ovarian cancer is planned for later this year. Healio spoke Cibula about the safety, efficacy and feasibility of dendritic cell-based immunotherapy and what he hopes to see in the upcoming phase 3 trial.
How do the results of SOV02 compare with other trials evaluating dendritic cell-based therapy in ovarian cancer?
Sotio’s technology of manufacturing dendritic cell-based cancer immunotherapy differs from all the previous approaches. It is based on the generation of fully-activated dendritic cells that present multiple tumor antigens derived from allogeneic ovarian cancer cell lines. This leads to the induction of a broad antitumor immune response targeting multiple targets on the tumor cells. It is hard to compare it to the clinical programs that were only targeting single-tumor antigens.
We do see consistent results with promising efficacy signals in both our phase 2 trials — SOV01 in the first-line setting (reported at ASCO 2018) and SOV02 in patients with the first relapse of ovarian cancer.
How does the safety and efficacy of dendritic cell-based immunotherapy compare with other ovarian cancer treatments?
In both phase 2 trials, DCVAC was associated with an excellent safety profile. There were virtually no serious adverse events that could potentially be related to the vaccine. DCVAC does not cause autoimmune-related adverse events that are typically associated with checkpoint inhibitors.
So far, significant improvement of OS in the SOV02 trial among patients with recurrent disease has not been shown with any other immuno-oncology treatment in ovarian cancer.
Please discuss the process of tailoring treatment for each patient. Will this approach be feasible in the real-world setting?
Scaling up autologous cell therapy approaches has certainly been a challenging task, as seen, for example, with [chimerical antigen receptor T-cell (CAR T)] programs. Feasibility of the approach has been proven by successful manufacturing and the treatment of more than 2,000 patients involved in various DCVAC clinical trials conducted by Sotio across the world, including those with NSCLC and prostate cancer. We believe that we would be able to scale up the manufacturing and logistics of DCVAC in case of successful outcomes of the registrational clinical trials.
There was a significant improvement in the main secondary endpoint of OS, but not the primary endpoint of PFS. How will this be addressed during the regulatory approval process?
Planned design of the registrational trial will have OS as a primary endpoint.
What questions do you hope will be answered in the phase 3 trial?
It is hypothesized that repeated administration of DCVAC, especially in the maintenance period after chemotherapy, is one feature facilitating efficacy. More doses of DCVAC will be administered and the treatment period will be prolonged in the phase 3 trial in comparison to both previous phase 2 trials. Therefore, we hope for an even better result. Also, any standard of care background therapy will be allowed, so an interaction of DCVAC with bevacizumab or PARP inhibitors will be tested.
References:
- Cibula D, et al. Abstract 35. Presented at: Society of Gynecologic Oncology Annual Meeting on Women’s Cancer; March 16-19, 2019; Honolulu.
- Rob L, et al. Abstract 5509. Presented at: ASCO Annual Meeting; June 1-5, 2018; Chicago.
- Sotio. Sotio DCVAC Product Candidates. https://www.sotio.com/pipeline/dcvac-product-candidates. Accessed April 22, 2019.
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