NCT03775486

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

A Phase II Randomized, Multi-Center, Double-Blind, Global 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 Platinum-Based Chemotherapy With Durvalumab in First Line Stage IV Non Small Cell Lung Cancer (ORION)

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 401 (actual)
• Sponsor: AstraZeneca · Industry
• Sex: All
• Age: 18 Years – 130 Years
• Healthy volunteers: Not accepted

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.

Detailed description

Adult patients with a histologically or cytologically documented advanced NSCLC not amenable to curative surgery or radiation with tumors that lack activation EGFR mutations and ALK fusions are eligible for enrollment. During the initial therapy phase, patients will receive treatment with Durvalumab along with the Investigator's choice of platinum-based doublet therapy for squamous NSCLC (nab-paclitaxel plus carboplatin or gemcitabine plus carboplatin/cisplatin) and non-squamous NSCLC (nab-paclitaxel plus carboplatin or pemetrexed plus carboplatin/cisplatin) for 4 cycles. Patients who have completed 4 cycles and not progressed throughout the initial therapy phase will be randomized in a 1:1 ratio into the maintenance phase of the study to receive either Durvalumab plus placebo or Durvalumab plus Olaparib maintenance therapy. Patients will receive maintenance treatment until specific discontinuation criteria are met, including clinical disease progression (as assessed by the Investigator) or RECIST 1.1-defined radiological Progressive Disease (PD), unacceptable toxicity, and withdrawal of consent. Tumor evaluation scans will be performed until objective disease progression as efficacy assessments. All patients will be followed for survival until the end of the study.

Conditions

• Non-small Cell Lung Cancer NSCLC

Interventions

Type	Name	Description
DRUG	Durvalumab	Initial therapy phase: IV infusion q3w for 4 cycles. Maintenance phase: IV infusion q4w.
DRUG	Placebo for Olaparib	Matching tablet
DRUG	Olaparib	150-mg tablets (2 × 150-mg tablets for 300-mg dose) 100-mg tablet available if dose reductions are required
DRUG	Nab-paclitaxel+carboplatin	Standard of Care chemotherapy (squamous and non-squamous patients)
DRUG	Gemcitabine+carboplatin	Standard of Care chemotherapy (squamous patients only)
DRUG	Pemetrexed+carboplatin	Standard of Care chemotherapy (non-squamous patients only)
DRUG	Gemcitabine+cisplatin	Standard of Care chemotherapy (squamous patients only)
DRUG	Pemetrexed+cisplatin	Standard of Care chemotherapy (non-squamous patients only)

Timeline

• Start date: 2018-12-21
• Primary completion: 2021-01-11
• Completion: 2026-09-27
• First posted: 2018-12-14
• Last updated: 2026-02-10
• Results posted: 2022-12-12

Locations

69 sites across 12 countries: United States, Belgium, Hungary, India, Japan, Mexico, Netherlands, Poland, Russia, South Korea, Ukraine, United Kingdom

Regulatory

• FDA-regulated drug study