Study of Durvalumab+Olaparib or Durvalumab After Treatment With Durvalumab and Chemotherapy in Patients With Lung Cancer (ORION)
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)
2 other identifiers
interventional
401
12 countries
68
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Dec 2018
Longer than P75 for phase_2
68 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 27, 2018
CompletedFirst Posted
Study publicly available on registry
December 14, 2018
CompletedStudy Start
First participant enrolled
December 21, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 11, 2021
CompletedResults Posted
Study results publicly available
December 12, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
September 27, 2026
ExpectedMay 1, 2026
April 1, 2026
2.1 years
November 27, 2018
July 4, 2022
April 30, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Progression-free Survival
Progression-free survival (PFS) based on investigator assessments according to Response Evaluation Criteria in Solid Tumours version 1.1. PFS is defined as time from date of randomization until the date of objective radiological disease progression using Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST 1.1) or death (by any cause in the absence of progression).
From randomization until date of objective radiological disease progression or death, or last evaluable assessment in the absence of progression, up to 18 months
Secondary Outcomes (11)
Overall Survival
From randomization until the date of death due to any cause, up to 18 months.
Objective Response Rate
From randomization until date of objective radiological disease progression or death, or last evaluable assessment in the absence of progression, up to 18 months
Duration of Response
From date of first documented response until objective radiological disease progression or death, up to 18 months.
Progression-free Survival in Homologous Recombination Repair Related Gene Mutation (HRRm) Population
From randomization until date of objective radiological disease progression or death, or last evaluable assessment in the absence of progression, up to 18 months
Concentration of Durvalumab
Assessed from start of initial therapy up to 2 years.
- +6 more secondary outcomes
Study Arms (2)
Durvalumab/Olaparib Combination Therapy
EXPERIMENTALDurvalumab/Olaparib Combination Therapy: Durvalumab/SoC chemotherapy (initial therapy phase) followed by Durvalumab/Olaparib (maintenance phase)
Durvalumab Monotherapy
EXPERIMENTALDurvalumab Monotherapy: Durvalumab/SoC chemotherapy (initial therapy phase) followed by Durvalumab/placebo (maintenance phase)
Interventions
Initial therapy phase: IV infusion q3w for 4 cycles. Maintenance phase: IV infusion q4w.
150-mg tablets (2 × 150-mg tablets for 300-mg dose) 100-mg tablet available if dose reductions are required
Standard of Care chemotherapy (squamous and non-squamous patients)
Standard of Care chemotherapy (squamous patients only)
Standard of Care chemotherapy (non-squamous patients only)
Standard of Care chemotherapy (squamous patients only)
Standard of Care chemotherapy (non-squamous patients only)
Eligibility Criteria
You may qualify if:
- \- Histologically or cytologically documented Stage IV NSCLC not amenable to curative surgery or radiation.
- Patients must have tumors that lack activating EGFR mutations and ALK fusions.
- (WHO)/(ECOG) performance status of 0 or 1
- No prior chemotherapy or any other systemic therapy for Stage IV NSCLC
- Adequate organ and marrow function without blood transfusions in the past 28 days,
- At least 1 tumor lesion, not previously irradiated, that can be accurately measured as per RECIST 1.1.
- Documented radiographic evidence of CR, PR, or Stable Disease (SD) as per Investigator-assessed RECIST 1.1 following 4 cycles of platinum-based chemotherapy.
- Creatinine Clearance (CrCl) ≥51 mL/min calculated by the investigator or designee using the Cockcroft-Gault equation or measured by 24-hour urine collection.
- Ability to swallow whole oral medications.
- All patients must provide a formalin-fixed, paraffin embedded tumor sample for tissue-based immunohistochemistry staining and DNA sequencing to determine PD-L1 expression, HRRm status, and other correlatives: either newly acquired or archival tumor samples (\<3 years old) are acceptable. If available, a newly acquired tumor biopsy, collected as part of routine clinical practice, is preferred. If not available, an archival sample taken \<3 years prior to screening is acceptable. If both an archival sample and a fresh tumor biopsy sample are available, both samples should be submitted for analysis and must be submitted as different samples using different accession numbers. Slides from different blocks cannot be mixed and submitted with the same kit.
You may not qualify if:
- Mixed small-cell lung cancer and sarcomatoid variant NSCLC histology.
- Prior exposure to any chemotherapy agents (except chemotherapy or chemoradiation for non-metastatic disease), polyadenosine 5'diphosphoribose \[poly (ADP ribose)\] polymerase (PARP) therapy, or immunomediated therapy
- Active or prior documented autoimmune or inflammatory disorders.
- Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment.
- Current or prior use of immunosuppressive medication within 14 days before the first dose of Investigational Product (IP)
- untreated (CNS) metastases and/or carcinomatous meningitis
- Active infection.
- Inability to complete 4 cycles of platinum-based chemotherapy for any reason or discontinuation of Durvalumab during initial therapy.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AstraZenecalead
Study Sites (68)
Research Site
Bonita Springs, Florida, 34135, United States
Research Site
St. Petersburg, Florida, 33705, United States
Research Site
Tallahassee, Florida, 32308-5304, United States
Research Site
West Palm Beach, Florida, 33401, United States
Research Site
Kansas City, Missouri, 64132, United States
Research Site
Bethlehem, Pennsylvania, 18015, United States
Research Site
Chattanooga, Tennessee, 37404, United States
Research Site
Nashville, Tennessee, 37203, United States
Research Site
Houston, Texas, 77090, United States
Research Site
Aalst, 9300, Belgium
Research Site
Leuven, 3000, Belgium
Research Site
Roeselare, 8800, Belgium
Research Site
Budapest, 1088, Hungary
Research Site
Budapest, 1122, Hungary
Research Site
Debrecen, 4032, Hungary
Research Site
Deszk, 6772, Hungary
Research Site
Farkasgyepü, 8582, Hungary
Research Site
Törökbálint, 2045, Hungary
Research Site
Ahmedabad, 380009, India
Research Site
Ahmedabad, 380053, India
Research Site
Jamnagar, 361008, India
Research Site
Kochi, 682026, India
Research Site
Mysuru, 570021, India
Research Site
Nashik, 422004, India
Research Site
Nashik, 422009, India
Research Site
Pune, 411001, India
Research Site
Thiruvananthapuram, 695011, India
Research Site
Chūōku, 104-0045, Japan
Research Site
Kanazawa, 920-8641, Japan
Research Site
Kurume-shi,, 830-0011, Japan
Research Site
Matsuyama, 791-0280, Japan
Research Site
Nagoya, 460-0001, Japan
Research Site
Sendai, 980-0873, Japan
Research Site
Sunto-gun, 411-8777, Japan
Research Site
Ube-shi, 755-0241, Japan
Research Site
Chihuahua City, 31200, Mexico
Research Site
Culiacán, 80230, Mexico
Research Site
San Luis Potosí City, 78250, Mexico
Research Site
Blaricum, 1261, Netherlands
Research Site
Harderwijk, 3844, Netherlands
Research Site
Tilburg, 5022 GC, Netherlands
Research Site
Bialystok, 15-540, Poland
Research Site
Lodz, 90-302, Poland
Research Site
Poznan, 60-693, Poland
Research Site
Prabuty, 82-550, Poland
Research Site
Arkhangelsk, 163045, Russia
Research Site
Chelyabinsk, 454092, Russia
Research Site
Kursk, 305524, Russia
Research Site
Moscow, 115478, Russia
Research Site
Nal'chik, 360000, Russia
Research Site
P. Herzen Moscow Oncology Rese, 125284, Russia
Research Site
Saint Petersburg, 197022, Russia
Research Site
Sochi, 354000, Russia
Research Site
Yaroslavl, 150054, Russia
Research Site
Dongjakgu, 07061, South Korea
Research Site
Goyang-si, 10408, South Korea
Research Site
Seodaemun-gu, 03722, South Korea
Research Site
Seoul, 05505, South Korea
Research Site
Seoul, 06351, South Korea
Research Site
Suweonsi Paldalgu, 16247, South Korea
Research Site
Dnipro, 49102, Ukraine
Research Site
Kharkiv Region, 61024, Ukraine
Research Site
Kirovohrad, 25006, Ukraine
Research Site
Odesa, 65055, Ukraine
Research Site
Uzhhorod, 88000, Ukraine
Research Site
Zaporizhzhia, 69059, Ukraine
Research Site
Dundee, DD1 9SY, United Kingdom
Research Site
Hull, HU6 7RX, United Kingdom
Related Publications (1)
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.
PMID: 37390980DERIVED
Related Links
MeSH Terms
Interventions
Results Point of Contact
- Title
- Global Clinical Lead
- Organization
- AstraZeneca
Study Officials
- PRINCIPAL INVESTIGATOR
Myung-Ju Ahn, MD
Sungkyunkwan University School of Medicine, 135-710, Seoul, Korea
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 27, 2018
First Posted
December 14, 2018
Study Start
December 21, 2018
Primary Completion
January 11, 2021
Study Completion (Estimated)
September 27, 2026
Last Updated
May 1, 2026
Results First Posted
December 12, 2022
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- Time Frame
- AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
- Access Criteria
- When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.