Claire Manuszak, BS, research technician, Center for Immuno-Oncology Immune Assessment Laboratory, Dana-Farber Cancer Institute, discusses a phase I study (NCT03495323) with prexasertib (LY2606368) and LY3300054 in ovarian cancer.

Investigators evaluated the CHK1 inhibitor and the PD-L1 inhibitor in 15 patients with advanced solid tumors, including those with high-grade serous ovarian cancer. Prexasertib is a checkpoint kinase I inhibitor and LY3300054 is a monoclonal antibody that targets PD-L1. In the single-center study, patients received the combination intravenously on days 1 and 15, says Manuszak. Patient samples were also collected and evaluated for activation and checkpoint markers.

The results, which were presented at the 2019 SITC Annual Meeting, showed that 7 patients achieved a response to the combination, says Manuszak, which is encouraging for such a difficult-to-treat patient population. The study is expected to complete in April 2024.

Videos

Claire Manuszak, BS, discusses a phase I study (NCT03495323) with prexasertib (LY2606368) and LY3300054 in ovarian cancer.

Phase I Study With Prexasertib and 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.

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

Claire Manuszak, BS

Articles

Phase I Study With Prexasertib and LY3300054 in Ovarian Cancer

The Rationale to Combine Prexasertib With LY3300054 in Ovarian Cancer