Resistance & Activating Mutations Diagnosed Among NSCLC Community Dwelling EGFR Mutation Positive Patients

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.

Inclusion Criteria:

- Provision of informed consent prior to any study-specific procedures

- Females and males >/= 18 years

- Primary diagnosis of NSCLC with evidence of disease progression during or following
treatment with an EGFR tyrosine kinase inhibitor (diagnosis of NSCLC that is confirmed
by cytology is acceptable)

- Willing to undergo tumor biopsy (e.g., excision, core biopsy, or endoscopic biopsy),
preferably of a progressing lesion, and provide blood and urine for biomarker testing

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2

Exclusion Criteria:

- Involvement in the planning and/or conduct of the study

- Prior treatment with osimertinib or another T790M directed therapy

- Current participation in another clinical study with an investigational product or
patients who plan to receive any treatment that is not FDA-approved for EGFR mutation
positive NSCLC at any time during the course of this study

- Use of any chemotherapeutic agent within 1 week of tissue, plasma, and urine sample
collection

- For women - currently pregnant or plan to become pregnant during the course of the
study: pre-menopausal women of childbearing potential must have a urine or serum
pregnancy test performed during the screening/enrollment period and prior to
initiating anti-cancer treatment

- Judgment by the investigator that the patient should not participate in the study due
to the patient being unlikely to comply with study procedures, restrictions, and
requirements, such as in the case of severe or uncontrolled systemic disease.