A Study of BGB324 in Combination With Erlotinib in Patients With Non-Small Cell Lung Cancer
- Zale Lipshy University Hospital
David Gerber, M.D.
A Multi-Center Open-Label Phase I/2 Study of BGB324 in Combination With Erlotinib in Patients With Stage IIIb or Stage IV Non-Small Cell Lung Cancer
A Phase I/2 multi-center open-label study of BGB324 in combination with erlotinib in patients with Stage IIIb or Stage IV non-small cell lung cancer. BGB324 is a potent selective small molecule inhibitor of Axl, a surface membrane protein kinase receptor which is connected with poor prognosis and acquired resistance to therapy.
This is a multi-center, multi-arm open-label Phase I/2 study that will be conducted at up to
11 clinical sites in the US.
Up to approximately 66 patients with histologically- or cytologically-confirmed Stage IIIb or Stage IV non-small cell lung cancer will receive BGB324 as a single agent (Run-in Cohort(mono therapy)) or in combination with erlotinib (Arms A, B, C).
Run-in Arm to establish the safety and tolerability of BGB324 administered as a single agent. BGB324 will be administered at a loading dose of 600 mg on Day 1 and Day 2 of Cycle 1, followed by 200 mg daily thereafter. After 6 patients have been dosed and safety established Arm A ( dose escalation arm) will be opened to confirm the BGB324 to be used in combination with erlotinib.
In Arm A the dose of BGB324 will be escalated in a standard 3+3 fashion until an MTD of the combination ( BGB324+ erlotinib) is established. The dose of BGB324 to be investigated in arm B and C will be confirmed upon recommendation of a Safety Review Committee.
Arm B and C will open in parallel and will investigate BGB324 in combination with erlotinib.
- 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
- Known EGFR mutation status
- Has been receiving erlotinib for treatment of NSCLC with erlotinib-related toxicities well-controlled and less than Grade 3 in severity at screening
- 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
- Pregnant or lactating
- Abnormal left ventricular ejection fraction (less than the lower limit of normal for a patient of that age at the treating institution or <45%)
- Treatment with any of the following: histamine receptor two inhibitors, protocol pump inhibitors or antacids within three days or five half-lives, whichever is longer
- History of an ischemic cardiac event including myocardial infarction within 3 months of study entry
- NSCLC with evidence of a centrally cavitating lesion
- Pulmonary hemorrhage or hemoptysis > 2.5 mL blood within six weeks unless cause has been addressed and is medically resolved
- Treatment with cytotoxic chemotherapy within the preceding four weeks
- Treatment with other non-cytotoxic agents for NSCLC in the preceding ten days or four terminal half-lives, whichever is shorter
- Congestive cardiac failure of >Grade 2 severity according to the 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 the last three months