Bemcentinib and Docetaxel in Treating Patients with Stage IV Non-small Cell Lung Cancer
This phase I trial studies the side effects and best dose of bemcentinib when given together with docetaxel in treating patients with stage IV non-small cell lung cancer. Bemcentinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving bemcentinib and docetaxel may work better in treating patients with non-small cell lung cancer.
- 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
- Measurable or evaluable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1
- 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
- Absolute neutrophil count (ANC) >= 1500 cells/uL
- Hemoglobin >= 9 g/dL
- Platelets >= 100,000/uL
- Serum creatinine =< 1.5 mg/dL or calculated creatinine clearance >= 50 mL/min using the Cockcroft-Gault equation
- Total bilirubin =< upper limit of normal (ULN)
- Alanine aminotransferase (ALT) =< 1.5 x ULN, aspartate aminotransferase (AST) =< 1.5 x ULN; ALT and AST =< 5 x ULN if documented liver metastases
- Previous treatment-associated toxicities resolved to Common Terminology Criteria for Adverse Events (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
- Pregnant or lactating
- Abnormal left ventricular ejection fraction on echocardiography (less than the lower limit of normal for a patient of that age at the treating institution or < 45%)
- History of an ischemic cardiac event including myocardial infarction within 3 months of study entry
- Peripheral neuropathy National Cancer Institute (NCI) CTCAE >= grade 2 at baseline
- Pulmonary hemorrhage or hemoptysis > 2.5 mL blood within 6 weeks (or within 2 weeks if source definitively treated [eg, radiation therapy or bronchoscopic procedure])
- Congestive cardiac failure of > grade 2 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 the last three months
- History or presence of sustained bradycardia (less than or equal to 60 beats per minute [BPM]) or history of symptomatic bradycardia, left bundle branch block, cardiac pacemaker or significant atrial tachyarrhythmias, as defined by the need for treatment
- Previous treatment with docetaxel or an Axl inhibitor
- Current treatment with agents that may prolong QT interval and may cause Torsade de Points which cannot be discontinued at least five half-lives prior to treatment
- Known family or personal history of long corrected QT (QTc) syndrome or ventricular arrhythmias including ventricular bigeminy
- Previous history of grade 3 or worse drug-induced QTc prolongation requiring treatment withdrawal
- Screening 12-lead electrocardiogram (ECG) with a measurable QTc interval according to Fridericia’s correction > 450 ms
- Ongoing infection requiring systemic treatment
- Inability to tolerate oral medication
- Impaired coagulation as evidenced by: * International normalized ratio (INR) > 1.5 times ULN, or * Activated partial thromboplastin time (aPTT) > 1.5 times ULN
- Clinically active existing gastrointestinal disease affecting drug absorption, such as celiac disease or Crohn’s disease
- Previous bowel resection anticipated to affect drug absorption
- Any evidence of severe or uncontrolled systemic conditions (e.g., severe hepatic impairment) or current unstable or uncompensated respiratory or cardiac conditions which makes it undesirable for the patient to participate in the study or which could jeopardize compliance with the protocol
- Treatment with any medication which is predominantly metabolized by CYP3A4 and has a narrow therapeutic index
- Active, uncontrolled central nervous system (CNS) disease
- Known active infection with human immunodeficiency virus (HIV), hepatitis B or C viruses (screening not required)
- Major surgery within 28 days prior to the start of BGB324, excluding skin biopsies and procedures for insertion of central venous access devices
- Treatment with more than 40 mg prednisolone (or equivalent dose of systemic corticosteroid) which cannot be discontinued up to one week prior to starting BGB324
Locations & Contacts
Contact: David Eric Gerber
Trial Objectives and Outline
I. To determine the safety and tolerability and recommended phase 2 dose (RP2D) of bemcentinib (BGB324) administered with the standard dose of docetaxel in patients with non-small cell lung cancer (NSCLC).
I. To determine the response rate, progression-free survival and overall survival of BGB324 therapy in combination with docetaxel in patients with NSCLC.
II. To determine pharmacokinetics and pharmacodynamics of BGB324 alone and in combination with docetaxel.
III. To assess the pharmacokinetics (PK) of docetaxel in combination with BGB324.
OUTLINE: This is a dose escalation study of bemcentinib.
Patients receive docetaxel intravenously (IV) over 1 hour on day 1 and bemcentinib orally (PO) daily on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 28 days and then every 4 months thereafter.
Trial Phase & Type
UT Southwestern / Simmons Cancer Center-Dallas
David Eric Gerber
Secondary IDs NCI-2016-01800, SCCC-06515
Clinicaltrials.gov ID NCT02922777