Study of Durvalumab+Olaparib or Durvalumab After Treatment With Durvalumab and Chemotherapy in Patients With Lung Cancer (ORION)

Summary

This is a randomized, double-blind, multi-center, global Phase II study to determine the efficacy and safety of Durvalumab plus Olaparib combination therapy compared with Durvalumab monotherapy as maintenance therapy in patients whose disease has not progressed following Standard of Care (SoC) platinum-based chemotherapy with Durvalumab as first-line treatment in patients with Stage IV non small-cell lung cancer (NSCLC) with tumors that lack activating epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) fusions.

Timeline

Start

2018-12-21

Primary completion

2021-01-11

Completion

2026-09-27

Outcome

Missed primary endpoint

registry analysis (other test); Durvalumab/Olaparib Combination Therapy vs Durvalumab/Placebo Therapy; p = 0.074; Hazard Ratio (HR) 0.76 (95% CI 0.57 to 1.02); Log Rank NCT03775486 ↗

paper Maintenance therapy with durvalumab in combination with olaparib was not associated with a statistically significant improvement in PFS versus durvalumab alone, although numerical improvement was observed. PMID 37390980 ↗

Publications

• Ahn MJ, Bondarenko I, Kalinka E, Cho BC, Sugawara S, Galffy G, Shim BY, Kislov N, Nagarkar R, Demedts I, Gans SJM, Mendoza Oliva D, Stewart R, Lai Z, Mann H, Shi X, Hussein M. Durvalumab in Combination With Olaparib Versus Durvalumab Alone as Maintenance Therapy in Metastatic NSCLC: The Phase 2 ORION Study. J Thorac Oncol. 2023 Nov;18(11):1594-1606. doi: 10.1016/j.jtho.2023.06.013. Epub 2023 Jun 29.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Durvalumab	Monoclonal antibody	1500 mg	Intravenous
Subject	Olaparib	Small molecule	300 mg	Oral
Background	Carboplatin	Small molecule	—	—
Background	Cisplatin	Other / unclassified	—	—
Background	Gemcitabine	Small molecule	—	—
Background	Nab-paclitaxel	Small molecule	—	—
Background	Pemetrexed	Small molecule	—	—

Indications