Study of Durvalumab+Olaparib or Durvalumab After Treatment With Durvalumab and Chemotherapy in Patients With Lung Cancer (ORION) (ORION)
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT03775486 |
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Recruitment Status :
Active, not recruiting
First Posted : December 14, 2018
Results First Posted : December 12, 2022
Last Update Posted : October 17, 2023
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Non-small Cell Lung Cancer NSCLC | Drug: Durvalumab Drug: Placebo for Olaparib Drug: Olaparib Drug: Nab-paclitaxel+carboplatin Drug: Gemcitabine+carboplatin Drug: Pemetrexed+carboplatin Drug: Gemcitabine+cisplatin Drug: Pemetrexed+cisplatin | Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 401 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Triple (Participant, Care Provider, Investigator) |
| Primary Purpose: | Treatment |
| 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) |
| Actual Study Start Date : | December 21, 2018 |
| Actual Primary Completion Date : | January 11, 2021 |
| Estimated Study Completion Date : | September 29, 2024 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Durvalumab/Olaparib Combination Therapy
Durvalumab/Olaparib Combination Therapy: Durvalumab/SoC chemotherapy (initial therapy phase) followed by Durvalumab/Olaparib (maintenance phase) |
Drug: Durvalumab
Initial therapy phase: IV infusion q3w for 4 cycles. Maintenance phase: IV infusion q4w.
Other Name: MEDI4736 (Durvalumab) Drug: Olaparib 150-mg tablets (2 × 150-mg tablets for 300-mg dose) 100-mg tablet available if dose reductions are required
Other Name: AZD2281 (Olaparib) 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) |
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Experimental: Durvalumab Monotherapy
Durvalumab Monotherapy: Durvalumab/SoC chemotherapy (initial therapy phase) followed by Durvalumab/placebo (maintenance phase)
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Drug: Durvalumab
Initial therapy phase: IV infusion q3w for 4 cycles. Maintenance phase: IV infusion q4w.
Other Name: MEDI4736 (Durvalumab) Drug: Placebo for Olaparib Matching tablet
Other Name: Placebo 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) |
- Progression-free Survival [ Time Frame: From randomization until date of objective radiological disease progression or death, or last evaluable assessment in the absence of progression, up to 18 months ]
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).
- Overall Survival [ Time Frame: From randomization until the date of death due to any cause, up to 18 months. ]
Overall survival (OS) across the maintenance phase.
OS is defined as time from date of randomization until the date of death by any cause
- Objective Response Rate [ Time Frame: From randomization until date of objective radiological disease progression or death, or last evaluable assessment in the absence of progression, up to 18 months ]Objective response rate (ORR) defined as number of participants with complete response (CR) or partial response (PR) after randomization
- Duration of Response [ Time Frame: From date of first documented response until objective radiological disease progression or death, up to 18 months. ]
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.
- Progression-free Survival in Homologous Recombination Repair Related Gene Mutation (HRRm) Population [ Time Frame: From randomization until date of objective radiological disease progression or death, or last evaluable assessment in the absence of progression, up to 18 months ]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).
- Concentration of Durvalumab [ Time Frame: Assessed from start of initial therapy up to 2 years. ]Concentration (pharmacokinetics) of durvalumab
- Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-Lung Cancer (LC)13 [ Time Frame: From randomization until date of objective radiological disease progression or death, or last evaluable assessment in the absence of progression, up to 18 months ]
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.
- Time to Deterioration in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-Lung Cancer (LC)13 [ Time Frame: From randomization until date of objective radiological disease progression or death, or last evaluable assessment in the absence of progression, up to 18 months ]
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.
- Change From Baseline in EORTC Quality of Life Questionnaire (QLQ) QLQ-C30 [ Time Frame: Includes all assessments occurring within the first 12 months of randomization or until disease progression, up to 18 months. ]
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.
- Time to Deterioration in EORTC Quality of Life Questionnaire (QLQ) QLQ-C30 [ Time Frame: From randomization until date of first symptom deterioration that is confirmed, up to 18 months. ]
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.
- Presence of Anti-drug Antibodies (ADAs) for Durvalumab [ Time Frame: Assessed from start of initial therapy up to 2 years. ]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
- Number of Participants With Treatment-Related Adverse Events [ Time Frame: From randomization until date of objective radiological disease progression or death, or last evaluable assessment in the absence of progression, up to 18 months ]Number of Participants with Treatment-Related Adverse Events as Assessed by Common Terminology Criteria for Adverse Events (CTCAE)
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years to 130 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- 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.
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.
Exclusion criteria
- 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.
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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03775486
Show 68 study locations
| Principal Investigator: | Myung-Ju Ahn, MD | Sungkyunkwan University School of Medicine, 135-710, Seoul, Korea |
Documents provided by AstraZeneca:
| Responsible Party: | AstraZeneca |
| ClinicalTrials.gov Identifier: | NCT03775486 |
| Other Study ID Numbers: |
D9102C00001 2018-003460-30 ( EudraCT Number ) |
| First Posted: | December 14, 2018 Key Record Dates |
| Results First Posted: | December 12, 2022 |
| Last Update Posted: | October 17, 2023 |
| Last Verified: | October 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | 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. |
| Supporting Materials: |
Study Protocol Statistical Analysis Plan (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. |
| URL: | https://astrazenecagroup-dt.pharmacm.com/DT/Home |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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NSCLC Durvalumab Olaparib Maintenance Homologous Recombination Repair (HRR) |
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Lung Neoplasms Carcinoma, Non-Small-Cell Lung Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms by Site Neoplasms Lung Diseases Respiratory Tract Diseases Carcinoma, Bronchogenic Bronchial Neoplasms Paclitaxel Cisplatin Carboplatin Gemcitabine Pemetrexed |
Durvalumab Olaparib Antibodies, Monoclonal Antineoplastic Agents, Phytogenic Antineoplastic Agents Tubulin Modulators Antimitotic Agents Mitosis Modulators Molecular Mechanisms of Pharmacological Action Antimetabolites, Antineoplastic Antimetabolites Enzyme Inhibitors Folic Acid Antagonists Nucleic Acid Synthesis Inhibitors Antineoplastic Agents, Immunological |