Non-small Cell Lung Cancer NSCLCPhase 2ORIONNCT03775486
Study of Durvalumab+Olaparib or Durvalumab After Treatment With Durvalumab and Chemotherapy in Patients With Lung Cancer (ORION)
A Phase 2 study testing Durvalumab, Olaparib and Nab-paclitaxel+carboplatin in people with Non-small Cell Lung Cancer NSCLC, run by AstraZeneca at 68 sites in 12 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 130 years
- Conditions the study is for
- Non-small Cell Lung Cancer NSCLC
- What is being tested?
- Durvalumab, Olaparib and Nab-paclitaxel+carboplatin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 401 participants
- Where
- 68 sitesin 12 countries
- Study dates
- 21 Dec 2018to 27 Sep 2026
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 130 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- Key Inclusion criteria for randomization to maintenance treatment:
- 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.
Who cannot join
- 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
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- Active infection.
- Exclusion criteria to be randomized to maintenance treatment:
- Inability to complete 4 cycles of platinum-based chemotherapy for any reason or discontinuation of Durvalumab during initial therapy.
Trial locations and contacts
68 sites in 12 countries.
68 sites in 12 countries
United States9 sites
Research Site
Bethlehem, Pennsylvania, 18015
Research Site
Bonita Springs, Florida, 34135
Research Site
Chattanooga, Tennessee, 37404
Research Site
Houston, Texas, 77090
Research Site
Kansas City, Missouri, 64132
Research Site
Nashville, Tennessee, 37203
Research Site
St. Petersburg, Florida, 33705
Research Site
Tallahassee, Florida, 32308-5304
Research Site
West Palm Beach, Florida, 33401
India9 sites
Research Site
Ahmedabad, 380009
Research Site
Ahmedabad, 380053
Research Site
Jamnagar, 361008
Research Site
Kochi, 682026
Research Site
Mysuru, 570021
Research Site
Nashik, 422004
Research Site
Nashik, 422009
Research Site
Pune, 411001
Research Site
Thiruvananthapuram, 695011
Russia9 sites
Research Site
Arkhangelsk, 163045
Research Site
Chelyabinsk, 454092
Research Site
Kursk, 305524
Research Site
Moscow, 115478
Research Site
Nal'chik, 360000
Research Site
P. Herzen Moscow Oncology Rese, 125284
Research Site
Saint Petersburg, 197022
Research Site
Sochi, 354000
Research Site
Yaroslavl, 150054
Japan8 sites
Research Site
Chūōku, 104-0045
Research Site
Kanazawa, 920-8641
Research Site
Kurume-shi,, 830-0011
Research Site
Matsuyama, 791-0280
Research Site
Nagoya, 460-0001
Research Site
Sendai, 980-0873
Research Site
Sunto-gun, 411-8777
Research Site
Ube-shi, 755-0241
Hungary6 sites
Research Site
Budapest, 1088
Research Site
Budapest, 1122
Research Site
Debrecen, 4032
Research Site
Deszk, 6772
Research Site
Farkasgyepü, 8582
Research Site
Törökbálint, 2045
South Korea6 sites
Research Site
Dongjakgu, 07061
Research Site
Goyang-si, 10408
Research Site
Seodaemun-gu, 03722
Research Site
Seoul, 05505
Research Site
Seoul, 06351
Research Site
Suweonsi Paldalgu, 16247
Ukraine6 sites
Research Site
Dnipro, 49102
Research Site
Kharkiv Region, 61024
Research Site
Kirovohrad, 25006
Research Site
Odesa, 65055
Research Site
Uzhhorod, 88000
Research Site
Zaporizhzhya, 69059
Poland4 sites
Research Site
Bialystok, 15-540
Research Site
Lodz, 90-302
Research Site
Poznan, 60-693
Research Site
Prabuty, 82-550
Belgium3 sites
Research Site
Aalst, 9300
Research Site
Leuven, 3000
Research Site
Roeselare, 8800
Mexico3 sites
Research Site
Chihuahua City, 31200
Research Site
Culiacán, 80230
Research Site
San Luis Potosí City, 78250
Netherlands3 sites
Research Site
Blaricum, 1261
Research Site
Harderwijk, 3844
Research Site
Tilburg, 5022 GC
United Kingdom2 sites
Research Site
Dundee, DD1 9SY
Research Site
Hull, HU6 7RX
About this study
Official title: 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)
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.
Read the 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
- Being tested
- Durvalumab, Placebo for Olaparib, Olaparib, Nab-paclitaxel+carboplatin, Gemcitabine+carboplatin
- Keywords
- NSCLC, Durvalumab, Olaparib, Maintenance, Homologous Recombination Repair (HRR)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DurvalumabDrug
Also called MEDI4736 (Durvalumab)
Initial therapy phase: IV infusion q3w for 4 cycles. Maintenance phase: IV infusion q4w.
Placebo for OlaparibDrug
Also called Placebo
Matching tablet
OlaparibDrug
Also called AZD2281 (Olaparib)
150-mg tablets (2 × 150-mg tablets for 300-mg dose) 100-mg tablet available if dose reductions are required
Nab-paclitaxel+carboplatinDrug
Standard of Care chemotherapy (squamous and non-squamous patients)
Gemcitabine+carboplatinDrug
Standard of Care chemotherapy (squamous patients only)
Pemetrexed+carboplatinDrug
Standard of Care chemotherapy (non-squamous patients only)
Gemcitabine+cisplatinDrug
Standard of Care chemotherapy (squamous patients only)
Pemetrexed+cisplatinDrug
Standard of Care chemotherapy (non-squamous patients only)
| Study group | Role | What they receive |
|---|---|---|
| Durvalumab/Olaparib Combination Therapy | Experimental | Durvalumab/Olaparib Combination Therapy:
Durvalumab/SoC chemotherapy (initial therapy phase) followed by Durvalumab/Olaparib (maintenance phase) Receives: Drug: Durvalumab; Drug: Olaparib; Drug: Nab-paclitaxel+carboplatin; Drug: Gemcitabine+carboplatin; Drug: Pemetrexed+carboplatin; Drug: Gemcitabine+cisplatin; Drug: Pemetrexed+cisplatin |
| Durvalumab Monotherapy | Experimental | Durvalumab Monotherapy: Durvalumab/SoC chemotherapy (initial therapy phase) followed by Durvalumab/placebo (maintenance phase) Receives: Drug: Durvalumab; Drug: Placebo for Olaparib; Drug: Nab-paclitaxel+carboplatin; Drug: Gemcitabine+carboplatin; Drug: Pemetrexed+carboplatin; Drug: Gemcitabine+cisplatin; Drug: Pemetrexed+cisplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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
Overall survival (OS) across the maintenance phase.
OS is defined as time from date of randomization until the date of death by any cause
Measured: From randomization until the date of death due to any cause, up to 18 months.
Objective Response Rate
Objective response rate (ORR) defined as number of participants with complete response (CR) or partial response (PR) after randomization
Measured: 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
Duration of response (DoR) defined as time from the date of first documented response following randomization until the first date of documented progression or death in the absence of disease progression.
Percentage of participants remaining in response at 3, 6, 9 and 12 months estimated using the Kaplan-Meier method.
Measured: 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
Progression-free survival in homologous recombination repair related gene mutation (HRRm) population defined as time from date of randomization until the date of objective radiological disease progression in HRRm population using Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST 1.1) or death (by any cause in the absence of progression).
Measured: 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
Concentration (pharmacokinetics) of durvalumab
Measured: Assessed from start of initial therapy up to 2 years.
Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-Lung Cancer (LC)13
Disease-related symptoms assessed by change from baseline (for maintenance phase) in EORTC QLQ-LC13. Average adjusted mean over first 11 cycles is presented.
The EORTC QLQ-LC13 was scored according to the published scoring manual. An outcome variable consisting of a score from 0 to 100 was derived for each of the symptom scales in the EORTC QLQ-LC13. Higher scores on symptom scales represent greater symptom severity.
Measured: From randomization until date of objective radiological disease progression or death, or last evaluable assessment in the absence of progression, up to 18 months
Time to Deterioration in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-Lung Cancer (LC)13
Disease-related symptoms assessed by time to deterioration (for maintenance phase) in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-Lung Cancer (LC)13.
Symptom deterioration is defined as an increase in the score from baseline of less than or equal to 10) that is confirmed at a subsequent assessment, or death (by any cause) in the absence of a clinically meaningful symptom deterioration.
NA is "not applicable". The upper confidence limit was not calculable because of an insufficient number of participants with events.
Measured: From randomization until date of objective radiological disease progression or death, or last evaluable assessment in the absence of progression, up to 18 months
Change From Baseline in EORTC Quality of Life Questionnaire (QLQ) QLQ-C30
Disease-related symptoms and health-related quality of life (HRQoL) assessed by change from baseline (for maintenance phase) in EORTC QLQ-C30. Average adjusted mean over first 11 cycles is presented.
The EORTC QLQ-C30 was scored according to the published scoring manual. An outcome variable consisting of a score from 0 to 100 was derived for each of the symptom scales, each of the function scales, and the global health status/QoL scale in the EORTC QLQ-C30. Higher scores on the global health status and function scales indicate better health status/function.
A high scale score represents a higher response level. Thus a high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / quality of life (QoL) represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems.
Measured: Includes all assessments occurring within the first 12 months of randomization or until disease progression, up to 18 months.
Time to Deterioration in EORTC Quality of Life Questionnaire (QLQ) QLQ-C30
Disease-related symptoms and health-related quality of life (HRQoL) assessed by time to deterioration (for maintenance phase) in EORTC QLQ-C30.
NA is "not applicable". The upper confidence limit was not calculable because of an insufficient number of participants with events.
Measured: From randomization until date of first symptom deterioration that is confirmed, up to 18 months.
Presence of Anti-drug Antibodies (ADAs) for Durvalumab
Presence of anti-drug antibodies (ADAs) for durvalumab, as assessed at 3, 6, 12, 16 and 20 weeks after start of treatment and every 12 weeks thereafter until 3 and 6 months after last dose of durvalumab
Measured: Assessed from start of initial therapy up to 2 years.
Number of Participants With Treatment-Related Adverse Events
Number of Participants with Treatment-Related Adverse Events as Assessed by Common Terminology Criteria for Adverse Events (CTCAE)
Measured: From randomization until date of objective radiological disease progression or death, or last evaluable assessment in the absence of progression, up to 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Dec 2018
- Study start21 Dec 2018
- Primary completion11 Jan 2021
- Study completion27 Sep 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Non-small Cell Lung Cancer NSCLCStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 401 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Myung-Ju Ahn, MD, Principal investigator, Sungkyunkwan University School of Medicine, 135-710, Seoul, Korea
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03775486
- Sponsor's protocol ID
- D9102C00001
- Other IDs
- 2018-003460-30, 2018
- Acronym
- ORION
- Status last verified
- Aug 2026
- First submitted
- 27 Nov 2018
- Last updated
- 11 Sep 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
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.
PubMed 37390980