Clinical Trials /

Study of AZD9291 Plus MEDI4736 Versus AZD9291 Monotherapy in NSCLC After Previous EGFR TKI Therapy in T790M Mutation Positive Tumours

NCT02454933

Description:

A Phase III, Multi-Centre, Open Label, Randomized Study to Assess the Efficacy and Safety of AZD9291 in Combination with MEDI4736 versus AZD9291 Monotherapy in patients with Locally Advanced or Metastatic Epidermal Growth Factor Receptor T790M mutation-positive Non-Small Cell Lung Cancer who have received Prior Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy

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

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

Study of AZD9291 Plus MEDI4736 Versus AZD9291 Monotherapy in <span class="go-doc-concept go-doc-disease">NSCLC</span> After Previous <span class="go-doc-concept go-doc-biomarker">EGFR</span> <span class="go-doc-concept go-doc-intervention">TKI</span> Therapy in T790M <span class="go-doc-concept go-doc-keyword">Mutation</span> Positive Tumours

Title

  • Brief Title: Study of AZD9291 Plus MEDI4736 Versus AZD9291 Monotherapy in NSCLC After Previous EGFR TKI Therapy in T790M Mutation Positive Tumours
  • Official Title: A Phase III, Multi-Centre, Open Label, Randomized Study to Assess the Efficacy and Safety of AZD9291 in Combination With MEDI4736 Versus AZD9291 Monotherapy in Patients With Locally Advanced or Metastatic Epidermal Growth Factor Receptor T790M Mutation-positive Non-Small Cell Lung Cancer Who Have Received Prior Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy (CAURAL)
  • Clinical Trial IDs

    NCT ID: NCT02454933

    ORG ID: D5165C00001

    Trial Conditions

    Locally Advanced or Metastatic EGFR T790M+ NSCLC

    Trial Interventions

    Drug Synonyms Arms
    AZD9291 MEDI4736 & AZD9291 Combination, AZD9291 Monotherapy
    MEDI4736 MEDI4736 & AZD9291 Combination

    Trial Purpose

    A Phase III, Multi-Centre, Open Label, Randomized Study to Assess the Efficacy and Safety of
    AZD9291 in Combination with MEDI4736 versus AZD9291 Monotherapy in patients with Locally
    Advanced or Metastatic Epidermal Growth Factor Receptor T790M mutation-positive Non-Small
    Cell Lung Cancer who have received Prior Epidermal Growth Factor Receptor Tyrosine Kinase
    Inhibitor Therapy

    Detailed Description

    This a phase III, Multi Centre, Open Label, Randomized, Study to Assess the Efficacy and
    Safety of AZD9291 (80 mg, orally, once daily) in Combination with MEDI4736 (10 mg/kg (IV)
    infusion q2w) versus AZD9291 Monotherapy (80 mg, orally, once daily) in patients with a
    confirmed diagnosis of Epidermal Growth Factor Receptor (EGFR) T790M mutation positive
    NSCLC, who have progressed following prior therapy with an approved Epidermal Growth Factor
    Receptor Tyrosine Kinase Inhibitor (EGFR-TKI) agent. The randomization will be stratified by
    previous lines of treatment (2nd or 3rd+) and ethnicity (Asian or Non-Asian). A mandatory
    biopsy will be needed for central testing of T790M mutation status following confirmed
    disease progression on the most recent treatment regimen. The primary objective of the study
    is to assess the efficacy of AZD9291 in combination with MEDI4736 versus AZD9291 monotherapy
    by assessment of Progression Free Survival (PFS) by investigators according to Response
    Evaluation Criteria in Solid Tumours version 1.1 (RECIST 1.1).

    Approximately 350 patients will be evaluated and will consist of 2 populations:

    1. 2nd line: patients who have progressed following an approved first-line EGFR-TKI
    treatment but who have not received further treatment.

    2. 3rd line or higher: patients who have progressed following prior therapy with an
    approved EGFR-TKI and an additional anti-cancer treatment. Patients may have also
    received additional lines of treatment.

    Trial Arms

    Name Type Description Interventions
    MEDI4736 & AZD9291 Combination Experimental 10mg/kg q2w (IV) infusion & once daily tablet 80 mg AZD9291, MEDI4736
    AZD9291 Monotherapy Experimental Once daily tablet 80 mg AZD9291

    Eligibility Criteria

    Inclusion Criteria:

    - Aged at least 18 years. Japan patients aged at least 20 years.

    - Locally advanced/metastatic NSCLC, not amenable to curative surgery or radiotherapy

    - Confirmation from a previous archival sample that the tumour harbours an EGFR
    mutation known to be associated with EGFR TKI sensitivity

    - Radiological documentation of disease progression while on a previous continuous
    treatment with an EGFR TKI. Additional other lines of therapy may have been given.
    All patients must have documented radiological progression on the last treatment
    administered prior to enrolling in the study.

    - Patients must have central lab confirmation of tumour T790M status from a biopsy
    taken after disease progression on the most recent treatment regimen. Only patients
    with T790M+ will be included in the study

    - At least one lesion, not previously irradiated and not chosen for biopsy during the
    study screening period, that can be accurately measured at baseline as 10mm in the
    longest diameter (except lymph nodes which must have short axis 15mm) with
    computerised tomography (CT) or magnetic resonance imaging (MRI) which is suitable
    for accurate repeated measurements

    - World Health Organisation (WHO) performance status 0-1 with no deterioration over the
    previous 2 weeks and a minimum life expectancy of 12 weeks

    - Females of child-bearing potential using contraception; negative pregnancy test

    Exclusion Criteria:

    - Treatment with an EGFR-TKI within 5x half-life of study entry; any cytotoxic
    chemotherapy, investigational agents or other anticancer drugs within 14 days of
    study entry; current treatment with potent inhibitors/inducers of cytochrome P450 3A4
    (CYP3A4); previous treatment with AZD9291 (or other agents specifically targeted
    against EGFR T790M mutation positive NSCLC); Prior neo-adjuvant or adjuvant
    chemotherapy treatment within 6 months of starting 1st EGFR TKI treatment; prior
    exposure to immune-mediated therapy including, but not limited to, other anti
    cytotoxic T-lymphocyte-associated antigen 4 (anti CTLA-4), anti- programmed cell
    death 1 (anti-PD-1), anti- programmed cell death ligand 1 (anti-PD-L1), and
    anti-programmed cell death ligand 2 (anti-PD-L2) antibodies, excluding therapeutic
    anticancer vaccines; radiotherapy treatment to more than 30% of the bone marrow or
    with a wide field of radiation within 4 weeks; major surgery within 4 weeks;

    - Current or prior use of immunosuppressive medication within 14 days before the first
    dose of MEDI4736 (excluding intranasal, inhaled, topical steroids, or local steroid
    injections)

    - Unresolved toxicities from prior therapy

    - History of active primary immunodeficiency

    - Unstable brain metastases or spinal cord compression

    - Severe/uncontrolled systemic diseases, including uncontrolled hypertension, renal
    transplant, bleeding diatheses or infection

    - Cardiac disease

    - Ophthalmological conditions

    - Refractory nausea/vomiting, chronic gastrointestinal diseases or bowel resection

    - Past history of interstitial lung disease (ILD), drug-induced ILD, radiation
    pneumonitis which required steroid treatment, or any evidence of clinically active
    interstitial lung disease.

    - History of another primary malignancy

    - Active or prior documented autoimmune or inflammatory disorders within the past 3
    years prior to the start of treatment

    - History of organ transplant that requires use of immunosuppressive medications

    - Known history of tuberculosis

    - Receipt of live, attenuated vaccine within 30 days prior to the first dose of
    MEDI4736

    - Inadequate bone marrow reserve or organ function

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    PFS according to RECIST 1.1

    Secondary Outcome Measures

    ORR according to RECIST 1.1

    DoR according to RECIST 1.1

    DCR according to RECIST 1.1

    Overall Survival

    Tumour shrinkage according to RECIST 1.1

    Number of subjects with Adverse Events as a measure of safety and tolerability of AZD9291 as a single agent and in combination with MEDI4736

    European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 items (EORTC QLQ-C30) & EORTC QLQ - Lung Cancer 13 items (EORTC QLQ LC13) measuring patients general cancer symptoms and functioning

    Trial Keywords

    Phase III Open Label Study; AZD9291 plus MEDI4736 versus AZD9291 Monotherapy; NSCLC After Previous EGFR TKI Therapy; T790M Mutation Positive Tumours.