The Phase 2 DOVACC collaboration study will investigate UV1, in combination with AstraZeneca’s immune checkpoint inhibitor Imfinzi (durvalumab) and PARP inhibitor Lynparza (olaparib), as a maintenance treatment for women with high-grade ovarian cancer who are responding to their second round of chemotherapy.
The trial will be conducted at over 30 clinical sites across 10 countries in Europe. Ultimovacs expects the first patient to be dosed by June, and top-line data to be available in 2023.
DOVACC is a collaborative enterprise involving Ultimovacs, AstraZeneca, the Nordic Society of Gynaecological Oncology – Clinical Trial Unit (NSGO-CTU), and the European Network of Gynaecological Oncological Trial Groups (ENGOT).
“The collaboration with the NSGO-CTU and ENGOT is exciting for us as they are very experienced with conducting clinical trials in the field of gynaecological oncology,” Jens Bjørheim, chief medical officer at Ultimovacs, said in a press release.
“Their expertise and network will support the recruitment of patients at multiple participating study sites across Europe,” Bjørheim said.
Ultimovacs entered the collaboration to test UV1, its proprietary universal cancer vaccine, in the randomized Phase 2 clinical trial, sponsored by the NSGO.
“Now that the formal collaboration with NSGO-CTU/ENGOT and AstraZeneca is in place and preparations for the study are well underway, I am happy to provide further details on the DOVACC Phase II clinical trial,” said Carlos de Sousa, CEO at Ultimovacs.
A total of 184 patients who responded partially or completely to their second-line platinum-based chemotherapy are expected to enter the DOVACC trial. Participants will be randomly assigned to receive either Lynparza alone (46 patients), Lynparza plus Imfinzi (46 patients), or a triple combination of UV1 with Lynparza and Imfinzi (92 patients).
Of note, participants in the trial must have not been exposed to a PARP inhibitor in previous treatments, though they may have received bevacizumab as their first-line maintenance treatment, the company said in a webcast.
The trial’s main goal is to assess whether the triple combo significantly extends the time in which patients are alive and without signs of disease progression as compared with Lynparza alone. The double combination arm is “not designed to give statistic answers, but to give us numeric understanding of the contribution of [Imfinzi] in this study,” Bjørheim said in the webcast.
Under the terms of the collaboration, Ultimovacs will provide the UV1 vaccine and AstraZeneca will provide both Imfinzi and Lynparza.
The UV1 vaccine works by promoting immune responses against human telomerase reverse transcriptase (hTERT), an enzyme present in over 80% of all cancer cell types.
hTERT is essential for the restoration and maintenance of telomeres, the protective caps at the ends of chromosomes. Typically, telomeres become shorter each time a cell divides, which limits their lifespan. Cancer cells, however, increase the production of hTERT to prevent the rapid shortening of their telomeres, therefore allowing them to continue dividing and proliferating.
UV1 was designed to induce a strong T-cell response, and is being developed as an “off-the-shelf” cancer vaccine. T-cells are a type of immune cell involved in the fight against cancer.
The combination of UV1 with the immune checkpoint inhibitor Imfinzi and the PARP inhibitor Lynparza aims to promote a stronger anti-cancer response through the use of medications with distinct mechanisms of action.
Imfinzi is a form of immunotherapy designed to target the PD-L1 protein on cancer cells and prevent its interaction with the PD-1 receptor on immune cells. As this interaction is normally used by cancer cells to avoid being “seen” and eliminated by the immune system, Imfinzi enables more effective immune responses against the cancer.
Lynparza, on the other hand, is a form of targeted therapy that blocks the activity of PARP enzymes, which are involved in DNA repair. By blocking these enzymes, PARP inhibitors like Lynparza prevent cancer cells from repairing their DNA, eventually eliminating them.
“A key benefit of UV1 is its safety profile, which enables a triple combination study with a PD-L1 inhibitor and now for the first time also with a PARP inhibitor, in an indication in desperate need of new treatment options,” de Sousa said.
“The evaluation of UV1, durvalumab and olaparib in this Phase II triple combination study is an important next step in changing the standard of care for patients with ovarian cancer,” said Mansoor Raza Mirza, medical director of the NSGO-CTU and chair of the ENGOT. “We look forward to working with Ultimovacs to reach our mutual goal.”
Ultimovacs also is testing its UV1 vaccine in combination with different immunotherapies in a broad clinical development program for several other cancers, including metastatic melanoma.