A Phase II Pilot Study of Anti‐ PD ‐ L1 , Durvalumab, and a PARP Inhibitor, Olaparib in Patients With Metastatic Triple‐Negative Breast Cancer With or Without Germline BRCA Mutation

ABSTRACT Background Immunostimulatory effects of PARP inhibitors could increase sensitivity to immune checkpoint inhibitors. The previous Phase II trial ( MEDIOLA ) reported clinical benefits of durvalumab and olaparib (D + O) in patients with germline BRCA ‐mutated ( gBRCAm ) HER2 ‐negative metastatic breast cancer. Yet, the clinical activity of D + O in germline BRCA wild‐type ( gBRCAwt ) triple‐negative breast cancer ( TNBC ) remains unknown. Methods This single‐arm Phase II study tested D + O in patients with metastatic TNBC . The primary objective was overall response rate ( ORR ). Secondary objectives were safety, disease control rate ( DCR ), progression‐free survival ( PFS ) and overall survival ( OS ). Based on gBRCA status, patients were assigned to either gBRCAwt or gBRCAm cohort and were treated with D (1500 mg iv q4w) and O (300 mg twice a day orally). Pretreatment fresh tissues and serial blood samples were collected for correlative studies. Results Fifteen patients (12 gBRCAwt and 3 gBRCAm ) were enrolled. gBRCAm and gBRCAwt cohorts are reported as a combined dataset because of small sample size due to COVID ‐19 and slow accrual. The median number of prior therapies was three (range 0–8). Among 14 RECIST ‐evaluable patients (11 gBRCAwt and 3 gBRCAm ), ORR was 28.6% (3 gBRCAm and 1 gBRCAwt ). DCR was 64.3% (3 gBRCAm and 6 gBRCAwt ). The median PFS and OS were 3.6 months (95% confidence interval CI : 1.8–5.7) and 10.7 months (95% CI : 5.9–38.9), respectively. There is one gBRCAm patient with ongoing durable PR (67.4+ months). There was no new safety concern. CD83 expression on Types 1 and 2 conventional dendritic cells in blood at baseline was low in the patients with PFS ≥ 4 months compared to those with PFS < 4 months. Conclusion Our study demonstrated modest clinical benefits of D + O with ORR of 28.6% in subsets of heavily pretreated TNBC . Further detailed classification of DCs to understand the predictive role of DCs and prospective validation in a large cohort is required. Trial Registration ClinicalTrials.gov identifier: NCT02484404