Study of AZD9291 Plus MEDI4736 Versus AZD9291 Monotherapy in NSCLC After Previous EGFR TKI Therapy in T790M Mutation Positive Tumours
Condition: Locally Advanced or Metastatic EGFR T790M+ NSCLC
Intervention: AZD9291; MEDI4736
Intervention description: Once daily tablet 80 mg; 10mg/kg q2w (IV) infusion
Intervention MeSH terms: Durvalumab; Osimertinib
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 29.0
Sex: All
Minimum age: 18 Years
Maximum age: 130 Years
Healthy volunteers: No
Keywords: Phase III Open Label Study; AZD9291 plus MEDI4736 versus AZD9291 Monotherapy; NSCLC After Previous EGFR TKI Therapy; T790M Mutation Positive Tumours.

Summary:

      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
    

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