Preclinical activity of sacituzumab govitecan in TROP2-positive low-grade serous ovarian cancer patient-derived xenograft models.

Abstract

Objective: Low-grade serous ovarian cancer is a rare epithelial ovarian cancer subtype characterized by high resistance to chemotherapy and an indolent disease course. The development of novel, effective, targeted treatments for recurrent, chemotherapy-resistant low-grade serous ovarian cancer remains an unmet medical need. We evaluated trophoblast cell-surface antigen 2 (TROP2) expression in a cohort of patients with low-grade serous ovarian cancer and assessed the preclinical activity of sacituzumab govitecan, an antibody-drug conjugate targeting TROP2, in vivo using a patient-derived xenograft (PDX) model.

Methods: TROP2 expression was evaluated in 26 patients with low-grade serous ovarian cancer using immunohistochemistry. The efficacy of sacituzumab govitecan was assessed in vivo in severe combined immunodeficiency mice using a TROP2-positive low-grade serous ovarian cancer PDX model established from a patient with disease resistant to chemotherapy, aromatase inhibitors, and MEK inhibitors.

Results: TROP2 expression was observed in all low-grade serous ovarian cancer cases, with 21 of 26 (81%) samples demonstrating moderate to strong expression. In vivo studies in mice demonstrated that sacituzumab govitecan significantly inhibited tumor growth in a chemotherapy-, aromatase inhibitor-, and MEK inhibitor-resistant low-grade serous ovarian cancer PDX model compared to control animals treated with vehicle/saline (p < .0001). Median survival for control mice was 25 days, while it was not reached by the end of the experiment (day 50) in animals treated with sacituzumab govitecan.

Conclusion: TROP2 is a novel biomarker highly expressed in low-grade serous ovarian cancer. Sacituzumab govitecan may represent a potentially effective new treatment option for patients with low-grade serous ovarian cancer progressing after standard treatment modalities. Further clinical trials in low-grade serous ovarian cancer treated with sacituzumab govitecan are warranted.