Resistance & Activating Mutations Diagnosed Among NSCLC Community Dwelling EGFR Mutation Positive Patients
Condition: Non-small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Study type: Observational

Summary: 
      The study is being done to determine if non-invasive testing (urine and plasma testing) is as
      effective as tissue testing in identifying epidermal growth factor receptor (EGFR) T790M
      mutation status. EGFR is a type of protein found on the surface of cells in the body. When
      this protein is mutated and becomes too active, it can lead to cancer growth. T790M is a
      mutation that develops in response to treatment of the EGFR mutation.

      Participating patients will have tumor tissue (via cobas test), as well as 2 plasma samples
      (via cobas and Guardant360 tests) and 1 urine sample (via Trovera test), tested for EGFR
      T790M mutation status. If the results of the cobas tissue and/or plasma test show that a
      patient is T790M positive, they will be treated according to standard of care, which may
      include treatment with osimertinib. Osimertinib is approved for use in the United States for
      the treatment of EGFR T790M mutation-positive non-small cell lung cancer (NSCLC).
    

Detailed description: 
      RADIANCE is an open-label, prospective biomarker study to assess analytic concordance between
      non-invasive testing (plasma and urine) and tissue testing for the EGFR T790M mutation. All
      patients will have tumor tissue (via cobas test) as well as 2 plasma samples (via cobas and
      Guardant360) and 1 urine sample (via Trovera) tested for the EGFR T790M mutation (Part 1).
      Patients who are confirmed T790M negative based on both cobas biomarker tests (tissue and
      plasma) will have completed the study. Patients who demonstrate T790M+ on cobas tissue and/or
      cobas plasma testing may choose to undergo treatment with osimertinib in consultation with
      their healthcare provider (no investigational product will be provided for this study) and
      will continue to Part 2. In case of insufficient samples for biomarker testing or invalid
      results from any of the 4 testing modalities, another sample may be acquired from the
      patient, if feasible, including the patient's decision to undergo a second biopsy. Failure of
      a patient to undergo a tissue, plasma, or urine sample collection for biomarker testing will
      result in their withdrawal from the study. If 1 or more samples are insufficient for testing
      or 1 or more of the test results are invalid, the patient may still qualify for the clinical
      outcomes part of the study (Part 2) as long as cobas tissue and/or cobas plasma test is
      T790M+ and the patient receives at least one dose of osimertinib.

      During Part 2 Follow-Up Visits will occur according to standard of care, but at least every
      12 weeks for the first 12 months of treatment. A Final Study Visit will occur at 18 months
      (Week 72 +/- 14 days) or upon early withdrawal.

      Statistical methods Sample size: The sample size is such to provide enough statistical
      precision for the primary endpoint. A sample size of 400 patients with evaluable biomarker
      test results for analytic concordance has been selected in order to achieve a precision of no
      more than ±5% around the estimated concordance rate. If a 15% inflation factor is applied
      (~70 patients) to this sample size to take into account those patients who may not be
      evaluable for concordance estimates, a total of approximately 470 patients will be enrolled.

      The Full Analysis Sets will include the following:

      Part 1: All patients in the study with cobas tissue, Guardant360 plasma, and Trovera urine
      test results.

      Part 2: Patients who demonstrate T790M+ cobas tissue and/or cobas plasma testing and were
      treated with at least 1 dose of osimertinib (i.e., all patients in Part 2).

      Safety analysis sets: The safety analysis sets will include the following:

      Part 1: All patients in the study from the time of informed consent until completion of Part
      1.

      Part 2: Patients who demonstrate T790M+ cobas tissue and/or cobas plasms testing and were
      treated with at least 1 dose of osimertinib (i.e., all patients in Part 2).

      The analyses of the data collected within this study will be descriptive only, with no formal
      statistical testing. Continuous variables will be summarized by the number of observations,
      mean, standard deviation, median, minimum, and maximum. Categorical variables will be
      summarized by frequency counts and percentages for each category. A Statistical Analysis Plan
      will be prepared and finalized prior to the first interim analysis, which will occur upon
      completion of the diagnostic analytic validity part of the study (Part 1). The concordance
      rate between non-invasive testing and cobas tissue testing will be presented as the point
      estimate together with the exact 95% confidence interval (CI) estimated using the
      Clopper-Pearson method. The ORR will be presented as the point estimate together with the
      exact 95% CI according to the Clopper-Pearson method. The duration of response (DoR) and
      progression-free survival (PFS) will be presented for all patients in Part 2, summarized
      using the Kaplan-Meier (K-M) method with associated K-M curves. The median DoR and PFS will
      be presented, as well as the rates at clinically relevant time points, together with the
      associated 95% CIs.
    

Intervention name(s): Other
Intervention type(s): Drug
Intervention description(s): Patients who are T790M positive via cobas plasma and/or cobas tissue testing during Part 1 will be treated per standard of care during Part 2, which may include osimertinib.
Other intervention name(s): Standard of Care
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        The study population for this trial is non-small cell lung cancer patients who will come
        primarily from the community oncology practice setting.
      
Biospecimen description: 
      Whole blood, urine, and tissue
    
Keywords: T790M mutation; EGFR epidermal growth factor receptor; non-invasive testing; lung cancer