Description:
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.
Title
- Brief Title: Study of Durvalumab+Olaparib or Durvalumab After Treatment With Durvalumab and Chemotherapy in Patients With Lung Cancer (ORION)
- 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)
Clinical Trial IDs
- ORG STUDY ID:
D9102C00001
- SECONDARY ID:
2018-003460-30
- NCT ID:
NCT03775486
Conditions
- Non-small Cell Lung Cancer NSCLC
Interventions
Drug | Synonyms | Arms |
---|
Durvalumab | MEDI4736 (Durvalumab) | Durvalumab Monotherapy |
Placebo for Olaparib | Placebo | Durvalumab Monotherapy |
Olaparib | AZD2281 (Olaparib) | Durvalumab/Olaparib Combination Therapy |
Nab-paclitaxel+carboplatin | | Durvalumab Monotherapy |
Gemcitabine+carboplatin | | Durvalumab Monotherapy |
Pemetrexed+carboplatin | | Durvalumab Monotherapy |
Gemcitabine+cisplatin | | Durvalumab Monotherapy |
Pemetrexed+cisplatin | | Durvalumab Monotherapy |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
Durvalumab/Olaparib Combination Therapy | Experimental | Durvalumab/Olaparib Combination Therapy:
Durvalumab/SoC chemotherapy (initial therapy phase) followed by Durvalumab/Olaparib (maintenance phase) | - Durvalumab
- Olaparib
- Nab-paclitaxel+carboplatin
- Gemcitabine+carboplatin
- Pemetrexed+carboplatin
- Gemcitabine+cisplatin
- Pemetrexed+cisplatin
|
Durvalumab Monotherapy | Experimental | Durvalumab Monotherapy: Durvalumab/SoC chemotherapy (initial therapy phase) followed by Durvalumab/placebo (maintenance phase) | - Durvalumab
- Placebo for Olaparib
- Nab-paclitaxel+carboplatin
- Gemcitabine+carboplatin
- Pemetrexed+carboplatin
- Gemcitabine+cisplatin
- Pemetrexed+cisplatin
|
Eligibility 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.
Maximum Eligible Age: | 130 Years |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Progression-free survival |
Time Frame: | Approximately 2 years after randomization |
Safety Issue: | |
Description: | 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
Measure: | Overall survival |
Time Frame: | Approximately 4 years after randomization |
Safety Issue: | |
Description: | Overall survival (OS) defined as time from date of randomization until the date of death by any cause. |
Measure: | Objective response rate |
Time Frame: | Approximately 2 years after randomization. |
Safety Issue: | |
Description: | Objective response rate (ORR) defined as percentage of patients with an Investigator-assessed of complete response (CR) or partial response (PR) after randomization. |
Measure: | Duration of response |
Time Frame: | Approximately 2 years after randomization. |
Safety Issue: | |
Description: | 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. |
Measure: | PFS in homologous recombination repair related gene mutation (HRRm) population |
Time Frame: | Approximately 2 years after randomization |
Safety Issue: | |
Description: | 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). |
Measure: | 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 |
Safety Issue: | |
Description: | Concentration of Durvalumab: Pharmacokinetic (PK) of Durvalumab |
Measure: | 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 |
Safety Issue: | |
Description: | Disease-related symptoms and HRQoL assessed by change from baseline and time to deterioration (for maintenance phase) in EORTC QLQ-LC13. |
Measure: | 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 |
Safety Issue: | |
Description: | Disease-related symptoms and HRQoL assessed by change from baseline and time to deterioration (for maintenance phase) in EORTC QLQ-C30 |
Measure: | 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 |
Safety Issue: | |
Description: | Presence of anti-drug antibodies (ADA) for Durvalumab. |
Measure: | '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 |
Safety Issue: | |
Description: | 'Number of Participants with Treatment-Related Adverse Events as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Active, not recruiting |
Lead Sponsor: | AstraZeneca |
Trial Keywords
- NSCLC
- Durvalumab
- Olaparib
- Maintenance
- Homologous Recombination Repair (HRR)
Last Updated
April 28, 2020