A Study of BGB324 (Bemcentinib) in Combination With Erlotinib in Patients With Non-Small Cell Lung Cancer

General Criteria

• Provision of written informed consent to participate in this investigational study.
• Histological or cytological confirmation of Stage IIIb or Stage IV (unresectable) NSCLC.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
• Age 18 years or older at the time of consent.
• Female participants of childbearing potential must have a negative serum pregnancy test within 7 days prior to taking their first dose of bemcentinib. Male participants and female participants 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 bemcentinib. Female participants are considered NOT to be 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.

Additional Inclusion Criteria for Run-in Cohort

• Has received previous systemic therapy for unresectable NSCLC.
• Has exhausted existing licensed therapies, or is unsuitable for treatment with existing licensed therapies for NSCLC.

Additional Inclusion Criteria for Arm A

• Known EGFR mutation status.
• Either:
• Has received ≥ 6 weeks historical treatment with erlotinib. Erlotinib treatment must be re started ≥ 1 week before the first dose of bemcentinib (Cycle 1, Day 1).

Or:

• Is currently receiving erlotinib treatment for NSCLC and will have received ≥ 6 weeks treatment at the time of the first dose of bemcentinib (Cycle 1, Day 1).
• Erlotinib-related toxicities being well-controlled and 2.5 mL blood within 6 weeks of consent unless cause has been addressed and is medically resolved.
• Congestive cardiac failure of >Class II severity according to the New York Heart Association (NYHA) defined as symptomatic at less than ordinary levels of activity.
• Unstable cardiac disease, including unstable angina or unstable hypertension, as defined by the need for change in medication for lack of disease control within 3 months of consent.
• History or presence of sustained bradycardia (≤ 60 bpm) or history of symptomatic bradycardia, left bundle branch block, cardiac pacemaker or significant atrial tachyarrhythmias, as defined by the need for treatment.

tachyarrhythmias, as defined by the need for treatment.

• Current treatment with agents that may prolong QT interval and may cause Torsade de Points which cannot be discontinued at least 2 weeks prior to treatment.
• Known family or personal history of long QTc syndrome or ventricular arrhythmias including ventricular bigeminy.
• Previous history of ≥ Grade 3 drug-induced QTc prolongation.
• Screening 12-lead triplicate electrocardiogram (ECG) with an average measurable interval utilizing Fridericia's correction (QTcF) >450 ms.
• Inadequate liver function as demonstrated by:
• Serum bilirubin ≥ 1.5 times the upper limit of normal range (ULN); or
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥2.5 times the ULN (up to 5 times the ULN in the presence of liver metastases).
• Inability to tolerate oral medication.
• Impaired coagulation as evidenced by:
• International normalized ratio (INR) >1.5 times ULN (or equivalent); or
• Activated partial thromboplastin time (aPTT) >1.5 times ULN.
• Existing gastrointestinal disease affecting drug absorption, such as celiac disease or Crohn's disease.
• Previous bowel resection that may impair study drug absorption.
• Impaired renal function as demonstrated by creatinine clearance of ≤ 50 mL/min determined by Cockcroft Gault formula.
• Absolute neutrophil count <1.5 x 109/L, h