Phase II AZD9291 Open Label Study in NSCLC After Previous EGFR TKI Therapy in EGFR and T790M Mutation Positive Tumours
Condition: Non Small Cell Lung Cancer
MeSH terms: Carcinoma, Non-Small-Cell Lung
Intervention: AZD9291
Intervention description: Once daily tablet 80 mg
Intervention MeSH terms: Osimertinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 210.0
Sex: All
Minimum age: 18 Years
Maximum age: 130 Years
Healthy volunteers: No
Keywords: Phase II, open label study; safety and efficacy of AZD9291; diagnosis of Epidermal Growth Factor Receptor mutation positive and T790M mutation positive NSCLC

Summary:

      A Phase II, Open Label, Single-arm Study to Assess the Safety and Efficacy of AZD9291 in
      Patients with Locally Advanced/Metastatic Non Small Cell Lung Cancer whose Disease has
      Progressed with Previous Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy
      and whose Tumours are Epidermal Growth Factor Receptor Mutation and T790M Mutation Positive
    

Eligibility criteria:

        Inclusion:

          -  Aged at least 18 years. Japan patients aged at least 20 years.

          -  Locally advanced/metastatic NSCLC not amenable to curative surgery or radiotherapy

          -  Radiological documentation of disease progression:

        following 1st line EGFR TKI treatment but who have not received further treatment OR
        following prior therapy with an EGFR TKI and a platinum-based doublet chemotherapy.
        Patients who received prior EGFR TKI and platinum-based doublet chemotherapy may have also
        received additional lines of treatment. All patients must have documented radiological
        progression on the last treatment administered prior to enrolling in the study.

          -  Disease progression following 1st line EGFR TKI treatment or following prior EGFR TKI
             and platinum-containing doublet chemotherapy.

          -  Confirmation that the tumour harbours an EGFR mutation known to be associated with
             EGFR TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q). Patients must
             have central confirmation of tumour T790M mutation positive status from a biopsy
             sample taken after confirmation of disease progression on the most recent treatment
             regimen.

          -  World Health Organisation (WHO) performance status 0-1 with no deterioration over the
             previous 2 weeks and a minimum life expectancy of 12 weeks.

          -  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.

          -  Females of child-bearing potential using contraception; negative pregnancy test.

        Exclusion:

          -  Treatment with an EGFR-TKI within 8 days of study entry; any cytotoxic chemotherapy,
             investigational agents or other anticancer drugs within 14 days of study entry;
             previous treatment with AZD9291 (or 3rd generation TKIs); major surgery within 4
             weeks; radiotherapy treatment to more than 30% of the bone marrow or with a wide field
             of radiation within 4 weeks; current treatment with potent inhibitors of CYP2C8 and
             potent inhibitors/inducers of CYP3A4.

          -  Unresolved toxicities from prior therapy.

          -  Unstable spinal cord compression/brain metastases.

          -  Severe/uncontrolled systemic diseases, including uncontrolled hypertension, bleeding
             diatheses or infection.

          -  Refractory nausea/vomiting, chronic gastrointestinal diseases or bowel resection.

          -  Cardiac disease.

          -  Past history of ILD, drug-induced ILD, radiation pneumonitis which required steroid
             treatment, or any evidence of clinically active interstitial lung disease.

          -  Inadequate bone marrow reserve or organ function.