- 18 years of age or older at screening; outside the U.S. and European Union, an older
limit could apply depending on local regulation (eg, 19 years and older for South
Korea and 20 years and older for Taiwan).
- Histologically or cytologically confirmed unresectable locally advanced (Stage IIIB)
or metastatic (Stage IV) NSCLC.
- Documented evidence of somatic activating mutation in EGFR (eg, G719X, exon 19
deletion, L858R, L861Q) in a tumor tissue sample. If a tissue sample is not available,
then EGFR mutation status may be determined from circulating tumor DNA obtained from a
blood sample using a validated or approved test kit.
- Phase 1: Subjects must have previously received and progressed on or after
treatment with an EGFR tyrosine kinase inhibitor (TKI). Additional lines of
systemic therapy including investigational agents for locally advanced or
metastatic NSCLC are allowed.
- Phase 2: Subjects must not have received more than 1 prior line of therapy for
locally advanced or metastatic NSCLC. First-line treatment must include an EGFR
TKI, and subjects must have documented disease progression during or following
treatment. Subjects with disease that progressed more than 6 months after
completion of neoadjuvant/adjuvant chemotherapy or chemoradiation therapy are
eligible if they received an EGFR TKI as first-line treatment for advanced NSCLC.
- Subjects must have evidence of a T790M mutation in tumor tissue or plasma
obtained after disease progression during or after treatment with an EGFR
TKI. T790M mutation status from a local laboratory is acceptable; however, a
tumor tissue sample or plasma sample suitable for centralized T790M mutation
analysis must be available.
- Radiographically measurable or evaluable disease per RECIST v1.1.
- Known CNS metastases, unless stable and asymptomatic. Subjects with CNS metastases may
be eligible for the study, provided:
- There is no evidence of new or enlarging CNS metastasis or new neurological
symptoms attributable to CNS metastases.
- Subjects who are receiving corticosteroids must be on a stable or decreasing dose
for at least 4 weeks before first dose of study treatment.
- Laboratory parameters outside the protocol-defined range.
- Clinically significant abnormalities found on an ECG.
- Clinically significant or uncontrolled cardiac disease.
- Past history of interstitial lung disease (ILD), drug induced ILD, radiation
pneumonitis that required steroid treatment, or any evidence of clinically active ILD.
- Current or previous other malignancy within 2 years of study entry, except cured basal
or squamous cell skin cancer, superficial bladder cancer, prostate intraepithelial
neoplasm, carcinoma in situ of the cervix, or other noninvasive malignancy.
- Concurrent anticancer therapy (eg, chemotherapy, radiation therapy, surgery,
immunotherapy, biologic therapy, or hormonal therapy).
- Any previous use of Janus kinase (JAK) inhibitor, osimertinib, or other EGFR-directed
therapy for T790M-mt NSCLC.