# Phase II proof-of-concept study of durvalumab and cediranib with and without olaparib in recurrent ovarian cancer

## TL;DR

This study tested drug combinations in recurrent ovarian cancer and found that immune and metabolic factors influence treatment response.

## Contribution

The study identifies immune and metabolic biomarkers linked to treatment response in platinum-resistant ovarian cancer.

## Key findings

- Objective response rates were 19.4% for D + O + C and 29.6% for D + C.
- Exceptional responders showed immune activation at baseline and metabolic activity in D + C.
- Cytoskeletal changes were observed in non-responding tumors.

## Abstract

Platinum-resistant epithelial ovarian cancer (EOC) represents a population with limited therapeutic options. We conducted a proof-of-concept, phase II single-center, multi-arm study of durvalumab plus cediranib (D + C) or durvalumab, cediranib, and olaparib (D + O + C) in recurrent EOC. Sixty-eight patients were enrolled (D + O + C [n = 39] and D + C [n = 29]). Pre- and on-treatment biopsies and blood samples were collected for translational studies. Objective response rate was 19.4% (95% CI: 8.2–36.0) in D + O + C and 29.6% (95% CI: 13.8–50.2) in D + C. Progression-free survival (PFS) was 4.5 months for both arms. Four exceptional responders (PFS ≥ 12 months) were observed in each arm. Pre-treatment transcriptomic analysis identified that patients with exceptional response or clinical benefit (PR + SD ≥ 4 months) in both D + O + C and D + C arms demonstrated strong immune activation at baseline while D + C additionally depends on metabolic activity for response. Conversely, cytoskeletal redistribution was seen in transcriptomic data from patient tumors without clinical benefit. These findings emphasize the importance of combining immune, metabolic and cytoskeletal profiling-based treatment strategies for the future clinical studies in recurrent EOC.