Study of Durvalumab+Olaparib or Durvalumab After Treatment With Durvalumab and Chemotherapy in Patients With Lung Cancer (ORION) (ORION)
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| ClinicalTrials.gov Identifier: NCT03775486 |
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Recruitment Status :
Active, not recruiting
First Posted : December 14, 2018
Last Update Posted : April 28, 2020
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Sponsor:
AstraZeneca
Information provided by (Responsible Party):
AstraZeneca
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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.
| 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 |
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.
| 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 |
| Estimated Primary Completion Date : | June 2, 2021 |
| Estimated Study Completion Date : | June 2, 2022 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Lung cancer
| 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) |
Primary Outcome Measures :
- Progression-free survival [ Time Frame: Approximately 2 years after randomization ]Progression-free survival (PFS) defined as time from date of randomization until the date of objective radiological disease progression using RECIST 1.1 or death (by any cause in the absence of progression).
Secondary Outcome Measures :
- Overall survival [ Time Frame: Approximately 4 years after randomization ]Overall survival (OS) defined as time from date of randomization until the date of death by any cause.
- Objective response rate [ Time Frame: Approximately 2 years after randomization. ]Objective response rate (ORR) defined as percentage of patients with an Investigator-assessed of complete response (CR) or partial response (PR) after randomization.
- Duration of response [ Time Frame: Approximately 2 years after randomization. ]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.
- PFS in homologous recombination repair related gene mutation (HRRm) population [ Time Frame: Approximately 2 years after randomization ]PFS in HRRm population defined as time from date of randomization until the date of objective radiological disease progression in HRRm population using RECIST 1.1 or death (by any cause in the absence of progression).
- Concentration of Durvalumab [ Time Frame: PK of Durvalumab will be assessed at 3, 6, 12, 16 and 20 weeks after start of treatment and every 12 weeks thereafter until 3 months after last dose of durvalumab ]Concentration of Durvalumab: Pharmacokinetic (PK) of Durvalumab
- Change from baseline and time to deterioration in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-Lung Cancer (LC)13 [ Time Frame: Health-related quality of life (HRQoL) will be assessed at 4 weeks after randomization and every 4 weeks thereafter until 3 months after treatment discontinuation ]Disease-related symptoms and HRQoL assessed by change from baseline and time to deterioration (for maintenance phase) in EORTC QLQ-LC13.
- Change from baseline and time to deterioration in EORTC Quality of Life Questionnaire (QLQ) QLQ-C30 [ Time Frame: Health-related quality of life (HRQoL) will be assessed at 4 weeks after randomization and every 4 weeks thereafter until 3 months after treatment discontinuation ]Disease-related symptoms and HRQoL assessed by change from baseline and time to deterioration (for maintenance phase) in EORTC QLQ-C30
- Presence of anti-drug antibodies (ADA) for Durvalumab [ Time Frame: ADA will be 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 ]Presence of anti-drug antibodies (ADA) for Durvalumab.
- 'Number of Participants with Treatment-Related Adverse Events as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) [ Time Frame: Approximately 2 years after randomization ]'Number of Participants with Treatment-Related Adverse Events as Assessed by Common Terminology Criteria for Adverse Events (CTCAE)
Information from the National Library of Medicine
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| Ages Eligible for Study: | 18 Years to 130 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
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.
Information from the National Library of Medicine
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
Locations
Show 68 study locations
Sponsors and Collaborators
AstraZeneca
Investigators
| Principal Investigator: | Myung-Ju Ahn, MD | Sungkyunkwan University School of Medicine, 135-710, Seoul, Korea |
| 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 |
| Last Update Posted: | April 28, 2020 |
| Last Verified: | April 2020 |
| 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 |
Keywords provided by AstraZeneca:
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NSCLC Durvalumab Olaparib Maintenance Homologous Recombination Repair (HRR) |
Additional relevant MeSH terms:
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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 Gemcitabine Paclitaxel Cisplatin Carboplatin Pemetrexed |
Durvalumab Olaparib Antibodies, Monoclonal Antineoplastic Agents, Phytogenic Antineoplastic Agents Tubulin Modulators Antimitotic Agents Mitosis Modulators Molecular Mechanisms of Pharmacological Action Antimetabolites, Antineoplastic Antimetabolites Antiviral Agents Anti-Infective Agents Enzyme Inhibitors Immunosuppressive Agents |