Phase 1 Trial of Dose Escalated BGB324 in Combination With Docetaxel for Previously Treated Advanced Non-small Cell Lung Cancer (NSCLC)
Overview
- Phase
- Phase 1
- Status
- Completed
- Enrollment
- 23
- Locations
- 2
- Primary Endpoint
- Determine the maximum tolerated dose of BGB324 in combination with docetaxel
Overview
Brief Summary
This study is being done to evaluate the safety of the investigational study drug, BGB324 when administered in combination with docetaxel, and to establish the maximum tolerated dose.
Detailed Description
Lung cancer remains the leading cause of cancer-related deaths worldwide with an estimated incidence of 1.6 million cases resulting in 1.4 million deaths in annually. Non-small-cell lung cancer (NSCLC) represents 80-85% of cases, and adenocarcinoma is the most common histology.2 The majority of NSCLC patients present with advanced or metastatic disease that is not amenable to surgical resection. Platinum-based combination chemotherapy has reached a therapeutic plateau with a median overall survival (OS) of 7.4 to 9.9 months.
BGB324 is a potent selective small molecule inhibitor of Axl, a surface membrane protein kinase receptor that is over-expressed in many metastatic solid tumors and has been identified as a marker of a poor prognosis in patients with non-small cell lung cancer (NSCLC).
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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
Exclusion Criteria
- Not provided
Arms & Interventions
BGB324 in combination with docetaxel
The dose of docetaxel will be 75 mg/m2 given IV every 21 days. The dose of BGB324 will be escalated in a standard 3+3 fashion until a maximum tolerated dose is determined.
Intervention: BGB324 (Drug)
BGB324 in combination with docetaxel
The dose of docetaxel will be 75 mg/m2 given IV every 21 days. The dose of BGB324 will be escalated in a standard 3+3 fashion until a maximum tolerated dose is determined.
Intervention: Docetaxel (Drug)
Outcomes
Primary Outcomes
Determine the maximum tolerated dose of BGB324 in combination with docetaxel
Time Frame: 42 days or 2 cycles of 21 days
Determine and recommended the Phase 2 dose of BGB324 administered with the standard dose of docetaxel in patients in NSCLC by pharmacodynamics and pharmacokinetic assessments.
Secondary Outcomes
No secondary outcomes reported
Investigators
David E Gerber
Professor, Internal Medicine
University of Texas Southwestern Medical Center