Phase 1 Trial of Dose Escalated BGB324 in Combination With Docetaxel for Previously Treated Advanced Non-small Cell Lung Cancer (NSCLC)

• A patient is eligible for the study if the following criteria are met:

• Provision of written informed consent to participate in this investigational study

• Histologically or cytologically confirmed advanced (stage 4, according to the American Joint Committee on Cancer \[AJCC\] Staging manual) NSCLC

• Up to three previous lines of therapy, of which one must have been a platinum-based doublet therapy and no more than two were cytotoxic chemotherapy.

• Radiographic disease recurrence or progression during or after the last line of chemotherapy

• Patients with known activating EGFR mutations or ALK rearrangements should have progressed after appropriate targeted treatment in addition to progressing during or after platinum-based doublet chemotherapy

• European Cooperative Oncology Group (ECOG) performance status 0 or 1

• Age 18 years or older

• Measurable or evaluable disease according to RECIST v1.1

• Previously treated brain metastases (surgery and/or radiation therapy) are eligible, provided that patients are asymptomatic and not requiring corticosteroids

⁃ The following minimum intervals are required between prior treatment and initiation of study therapy:

⁃ Cytotoxic chemotherapy: 3 weeks Molecularly targeted therapy or immunotherapy: 2 weeks Conventional fractionated radiation therapy: 2 weeks Stereotactic radiation therapy: 1 week Major surgery: 3 weeks

⁃ Adequate hematologic function (absolute neutrophil count \[ANC\] ≥ 1500 cells/µL; hemoglobin ≥ 9 g/dL; platelets ≥ 100,000/µL

⁃ Adequate renal function (serum creatinine ≤ 1.5 mg/dL or calculated creatinine clearance ≥ 50 mL/min using the Cockcroft-Gault equation)

⁃ Adequate hepatic function: total bilirubin ≤ upper limit of normal \[ULN\], alanine aminotransferase \[ALT\] ≤ 1.5 x ULN, aspartate aminotransferase \[AST\] ≤ 1.5 x ULN). ALT and AST ≤ 5x ULN if documented liver metastases

⁃ Previous treatment-associated toxicities resolved to CTCAE grade ≤2 (except alopecia)

⁃ Adequate archival tissue (10-15 slides, or 5 slides with 3 sections per slide) for biomarker analysis

⁃ Female patients of childbearing potential must have a negative serum pregnancy test within 7 days prior to taking their first dose of BGB324. Male patients and female patients of reproductive potential must agree to practice highly effective methods of contraception (such as hormonal implants, combined oral contraceptives, injectable contraceptives, intrauterine device with hormone spirals, total sexual abstinence, vasectomy) throughout the study and for ≥3 months after the last dose of BGB324. Female patients are considered NOT of childbearing potential if they have a history of surgical sterility, including tubal ligation, or evidence of post-menopausal status defined as any of the following:

∙ Natural menopause with last menses \>1 year ago

‣ Radiation induced oophorectomy with last menses \>1 year ago

‣ Chemotherapy induced menopause with last menses \>1 year ago