The Rationale to Combine Prexasertib With LY3300054 in Ovarian Cancer

Claire Manuszak, BS, research technician, Dana-Farber Cancer Institute, discusses the rationale to combine prexasertib (LY2606368) and LY3300054 in patients with high-grade serous ovarian cancer.

The rationale for the phase I combination study of the CHK1 inhibitor and the anti—PD-L1 agent is, by combining a targeted therapy and immunotherapy, a possible treatment for patients with ovarian cancer and other advanced solid tumors will be discovered, explained Manuszak. By inhibiting PD-L1, apoptosis of lymphocytes and tumors cells can occur. Those tumor antigens can then be released into the immune system, says Manuszak.

In combination with the tumor antigens, PD-L1 inhibition allows for better antigen presentation and unleashes an immune cell response, which will better target tumor cells with checkpoint inhibitor therapy.

The study also included a T-cell subset analysis, in which researchers analyzed the T-cells for their activation memory markers. With this activation, researchers hope that the combination therapy with the PD-L1 antibody will show what T cells are activated. T-cell activation can target the tumor site better and overall T-cell activation will, hopefully, lead to better overall tumor targeting and a decrease in tumor size, concludes Manuszak.