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.
Unknown status
Phase 1/Phase 2
| Drug | Synonyms | Arms |
|---|---|---|
| erlotinib | Tarceva | Arm A |
| BGB324 | Arm A |
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.
| Name | Type | Description | Interventions |
|---|---|---|---|
| Arm A | Active Comparator | designed to determine the maximum dose of BGB324 that can be safely administered in combination with erlotinib administered at the approved oral dose level of 150 mg daily. It is anticipated that a maximum of three BGB324 dose levels will be evaluated, with up to approximately 18 patients enrolled. In the absence of unacceptable toxicity, patients will be allowed to continue receiving BGB324 in combination with erlotinib until disease progression.- (Arm completed) |
|
| Arm B | Active Comparator | will incorporate a Simon-like two-stage design with relaxed stopping for futility to evaluate the safety, pharmacokinetics and clinical activity of BGB324 in combination with erlotinib in patients with an activating EGFR mutation who have progressed after receiving prior erlotinib.( Open to enrolment) |
|
| Arm C | Active Comparator | will evaluate the safety, pharmacodynamics and clinical activity of BGB324 when administered in combination with erlotinib in patients with an activating EGFR mutation who have received at least twelve weeks of erlotinib without disease progression.(Open to enrolment) |
|
| Run in Arm | Other | The primary goal of the Run-in Cohort is to establish the safety and tolerability of BGB324 administered as a single agent. Eligible patients will have either exhausted existing licensed therapies or be unsuitable for treatment with existing licensed therapies for NSCLC. 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 (Arm completed) |
|
Inclusion 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
- 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
Exclusion Criteria:
- 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
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
| Measure: | History of an ischemic cardiac event including myocardial infarction |
| Time Frame: | within 3 months of study entry |
| Safety Issue: | |
| Description: |
| Phase: | Phase 1/Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Unknown status |
| Lead Sponsor: | BerGenBio ASA |
July 6, 2017
