Clinical Trials /

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

NCT03775486

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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

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

DrugSynonymsArms
DurvalumabMEDI4736 (Durvalumab)Durvalumab/Olaparib Combination Therapy
Placebo for OlaparibPlaceboDurvalumab Monotherapy
OlaparibAZD2281 (Olaparib)Durvalumab/Olaparib Combination Therapy
Nab-paclitaxel+carboplatinDurvalumab/Olaparib Combination Therapy
Gemcitabine+carboplatinDurvalumab/Olaparib Combination Therapy
Pemetrexed+carboplatinDurvalumab/Olaparib Combination Therapy
Gemcitabine+cisplatinDurvalumab/Olaparib Combination Therapy
Pemetrexed+cisplatinDurvalumab/Olaparib Combination Therapy

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

NameTypeDescriptionInterventions
Durvalumab/Olaparib Combination TherapyExperimentalDurvalumab/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 MonotherapyExperimentalDurvalumab 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 Cockcroft-Gault equation or
             measured by 24-hour urine collection.

          -  Ability to swallow whole oral medications.

        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 3 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 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 (for maintenance phase) in EORTC QLQ-LC13.
Measure:Change from baseline 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 (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:Not yet recruiting
Lead Sponsor:AstraZeneca

Trial Keywords

  • NSCLC
  • Durvalumab
  • Olaparib
  • Maintenance
  • Homologous Recombination Repair (HRR)

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