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Study of Durvalumab+Olaparib or Durvalumab After Treatment With Durvalumab and Chemotherapy in Patients With Lung Cancer (ORION)

Sponsor
AstraZeneca (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT03775486
Collaborator
(none)
401
Enrollment
68
Locations
2
Arms
41.4
Anticipated Duration (Months)
5.9
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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
Phase 2

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.

Study Design

Study Type:
Interventional
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 :
Dec 21, 2018
Actual Primary Completion Date :
Jan 11, 2021
Anticipated Study Completion Date :
Jun 2, 2022

Arms and Interventions

Arm Intervention/Treatment
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 Names:
  • 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 Names:
  • 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)
    Experimental: Durvalumab Monotherapy

    Durvalumab Monotherapy: Durvalumab/SoC chemotherapy (initial therapy phase) followed by Durvalumab/placebo (maintenance phase)

    Drug: Durvalumab
    Initial therapy phase: IV infusion q3w for 4 cycles. Maintenance phase: IV infusion q4w.
    Other Names:
  • MEDI4736 (Durvalumab)

    • Drug: Placebo for Olaparib
    Matching tablet
    Other Names:
  • 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)

    Outcome Measures

    Primary Outcome Measures

    1. Progression-free survival [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

    1. Overall survival [Approximately 4 years after randomization]

      Overall survival (OS) defined as time from date of randomization until the date of death by any cause.

    2. Objective response rate [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.

    3. Duration of response [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.

    4. PFS in homologous recombination repair related gene mutation (HRRm) population [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).

    5. Concentration of Durvalumab [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

    6. 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 [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.

    7. Change from baseline and time to deterioration in EORTC Quality of Life Questionnaire (QLQ) QLQ-C30 [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

    8. Presence of anti-drug antibodies (ADA) for Durvalumab [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.

    9. 'Number of Participants with Treatment-Related Adverse Events as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) [Approximately 2 years after randomization]

      'Number of Participants with Treatment-Related Adverse Events as Assessed by Common Terminology Criteria for Adverse Events (CTCAE)

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 130 Years
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Research Site Bonita Springs Florida United States 34135
    2 Research Site Saint Petersburg Florida United States 33705
    3 Research Site Tallahassee Florida United States 32308-5304
    4 Research Site West Palm Beach Florida United States 33401
    5 Research Site Kansas City Missouri United States 64132
    6 Research Site Bethlehem Pennsylvania United States 18015
    7 Research Site Chattanooga Tennessee United States 37404
    8 Research Site Nashville Tennessee United States 37203
    9 Research Site Houston Texas United States 77090
    10 Research Site Aalst Belgium 9300
    11 Research Site Leuven Belgium 3000
    12 Research Site Roeselare Belgium 8800
    13 Research Site Budapest Hungary 1088
    14 Research Site Budapest Hungary 1122
    15 Research Site Debrecen Hungary 4032
    16 Research Site Deszk Hungary 6772
    17 Research Site Farkasgyepü Hungary 8582
    18 Research Site Törökbálint Hungary 2045
    19 Research Site Ahmedabad India 380009
    20 Research Site Ahmedabad India 380053
    21 Research Site Jamnagar India 361008
    22 Research Site Kochi India 682026
    23 Research Site Mysuru India 570021
    24 Research Site Nashik India 422004
    25 Research Site Nashik India 422005
    26 Research Site Pune India 411001
    27 Research Site Thiruvananthapuram India 695011
    28 Research Site Chuo-ku Japan 104-0045
    29 Research Site Kanazawa-shi Japan 920-8641
    30 Research Site Kurume-shi, Japan 830-0011
    31 Research Site Matsuyama-shi Japan 791-0280
    32 Research Site Nagoya-shi Japan 460-0001
    33 Research Site Sendai-shi Japan 980-0873
    34 Research Site Sunto-gun Japan 411-8777
    35 Research Site Ube-shi Japan 755-0241
    36 Research Site Dongjakgu Korea, Republic of 07061
    37 Research Site Goyang-si Korea, Republic of 10408
    38 Research Site Seodaemun-gu Korea, Republic of 03722
    39 Research Site Seoul Korea, Republic of 05505
    40 Research Site Seoul Korea, Republic of 06351
    41 Research Site Suweonsi Paldalgu Korea, Republic of 16247
    42 Research Site Chihuahua Mexico 31200
    43 Research Site Culiacan Mexico 80230
    44 Research Site San Luis Potosí Mexico 78250
    45 Research Site Blaricum Netherlands 1261
    46 Research Site Harderwijk Netherlands 3844
    47 Research Site Tilburg Netherlands 5022 GC
    48 Research Site Białystok Poland 15-540
    49 Research Site Poznan Poland 60-693
    50 Research Site Prabuty Poland 82-550
    51 Research Site Łódź Poland 90-302
    52 Research Site Arkhangelsk Russian Federation 163045
    53 Research Site Chelyabinsk Russian Federation 454092
    54 Research Site Kursk Russian Federation 305524
    55 Research Site Moscow Russian Federation 115478
    56 Research Site Nal'chik Russian Federation 360000
    57 Research Site P. Herzen Moscow Oncology Rese Russian Federation 125284
    58 Research Site Sochi Russian Federation 354000
    59 Research Site St. Petersburg Russian Federation 197022
    60 Research Site Yaroslavl Russian Federation 150054
    61 Research Site Dnipro Ukraine 49102
    62 Research Site Kharkiv Region Ukraine 61024
    63 Research Site Kirovohrad Ukraine 25006
    64 Research Site Odesa Ukraine 65055
    65 Research Site Uzhhorod Ukraine 88000
    66 Research Site Zaporizhzhia Ukraine 69059
    67 Research Site Dundee United Kingdom DD1 9SY
    68 Research Site Hull United Kingdom HU6 7RX

    Sponsors and Collaborators

    • AstraZeneca

    Investigators

    • Principal Investigator: Myung-Ju Ahn, MD, Sungkyunkwan University School of Medicine, 135-710, Seoul, Korea

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    AstraZeneca
    ClinicalTrials.gov Identifier:
    NCT03775486
    Other Study ID Numbers:
    • D9102C00001
    • 2018-003460-30
    First Posted:
    Dec 14, 2018
    Last Update Posted:
    Apr 26, 2022
    Last Verified:
    Apr 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by AstraZeneca
    NSCLC
    Durvalumab
    Olaparib
    Maintenance
    Homologous Recombination Repair (HRR)
    Additional relevant MeSH terms:
    Lung Neoplasms
    Carcinoma, Non-Small-Cell Lung
    Gemcitabine
    Paclitaxel
    Cisplatin
    Carboplatin
    Pemetrexed
    Durvalumab
    Olaparib
    Antibodies, Monoclonal

    Study Results

    No Results Posted as of Apr 26, 2022