| Eligibility |
Inclusion Criteria:
1. At least = 18 years of age (male or female) at the time of signing the informed
consent form.
2. ECOG performance status of 0 to 1.
3. Patients with:
Phase 2 only:
• Advanced or metastatic NSCLC failing platinum-based therapy
Phase 3 only:
- Advanced or metastatic breast cancer, who have failed < 5 prior lines of
chemotherapy (Note that study treatment may be the first chemotherapy treatment
for advanced or metastatic cancer)
- locally advanced or metastatic NSCLC after platinum therapy failure
- HRPC (Note that study treatment may be the first chemotherapy treatment)
4. Pathology confirmation of cancer is required.
5. Patients with = 1 of the following risk factors, at the initiation of docetaxel
chemotherapy, that would require neutropenia prophylaxis per National Comprehensive
Cancer Network (NCCN) guidelines (version 2, 2016):
- Prior chemotherapy or radiation treatment
- Bone marrow involvement by tumor
- Surgery and/or open wounds within 4 weeks of first administration of study drug
- Age > 65 years of age and receiving full chemotherapy dose intensity
6. Life expectancy of 3 months or more.
7. The following laboratory results assessed within 14 days prior to study drug
administration:
- Hemoglobin >/= 9 g/dL independent of transfusion or growth factor support
- Absolute neutrophil count (ANC) >/= 1.5 x 10**9/L independent of growth factor
support
- Serum total bilirubin </= 1.5 times the upper limit normal (ULN), unless the
patient has a diagnosis of Gilbert's disease, in which case direct bilirubin </=
1.5 times ULN of the direct bilirubin.
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) </= 2.5 x ULN
(</= 1.5 x ULN if alkaline phosphatase is > 2.5 x ULN)
- Serum creatinine </= 1.5 x ULN
Note: Results are from the central laboratory. Local laboratory results may be
accepted on a case by case basis after discussion with the Medical Monitor, however in
this case central laboratories must also be taken within the screening time window.
8. Prothrombin time (PT)/International Normalized Ratio (INR) = 1.5 × upper limit of
normal (ULN), activated partial thromboplastin time (PTT) = 1.5 × ULN, based on
central laboratory results.
9. Female subjects of childbearing potential have a negative pregnancy test at screening.
Females of childbearing potential are defined as sexually mature women without prior
hysterectomy or who have had any evidence of menses in the past 12 months. However,
women who have been amenorrhoeic for 12 or more months are still considered to be of
childbearing potential if the amenorrhea is possibly due to prior chemotherapy,
anti-estrogens, or ovarian suppression.
- Women of childbearing potential (i.e., menstruating women) must have a negative
urine pregnancy test (positive urine tests are to be confirmed by serum test)
documented within the 24-hour period prior to the first dose of study drug.
- Sexually active women of childbearing potential enrolled in the study must agree
to use two forms of accepted methods of contraception during the course of the
study and for 3 months after their last dose of study drug. Effective birth
control includes (a) intrauterine device (IUD) plus one barrier method; (b) on
stable doses of hormonal contraception for at least 3 months (e.g., oral,
injectable, implant, transdermal) plus one barrier method; (c) 2 barrier methods.
Effective barrier methods are male or female condoms, diaphragms, and spermicides
(creams or gels that contain a chemical to kill sperm); or (d) a vasectomized
partner.
- For male patients who are sexually active and who are partners of premenopausal
women: agreement to use two forms of contraception during the treatment period
and for at least 3 months after the last dose of study drug.
Exclusion Criteria:
1. History of myelogenous leukemia, myelodysplastic syndrome or concomitant sickle cell
disease.
2. Received chemotherapy within 4 weeks prior to the first dose of study drug.
3. Received prior docetaxel treatment, except adjuvant docetaxel given > 1 year prior to
first dose of study drug
4. Phase 3 only: Received >/= 5 lines of cytotoxic chemotherapy for advanced or
metastatic breast cancer (adjuvant chemotherapy will count as one line of
chemotherapy, and any hormonal or biological, non conjugate therapy [e.g.,
trastuzumab] will not count as a line of therapy).
5. Current use of strong cytochrome P450 (CYP) 3A4 inhibitors, within 3 days of the first
administration of study drug, and 7 days after treatment with taxanes OR requires use
of strong CYP3A4 inhibitors
6. Received an investigational agent or tumor vaccine within 2 weeks before the first
dose of study drug; patients must have recovered from toxicity of prior treatment and
have no > Grade 1 CTCAE (v4.03) treatment emergent AEs.
7. Receiving any concurrent anticancer therapies (except continued hormonal treatment).
8. Received a prior bone marrow or stem cell transplant.
9. Has a co-existing active infection or received systemic anti-infective treatment
within 72 hours before the first dose of study drug.
10. Prior radiation therapy within the 4 weeks before the first dose of study drug.
11. Prior use of pegfilgrastim or filgrastim within 4 weeks before the first dose of study
drug.
12. Presence of any serious or uncontrolled illness including, but not limited to:
uncontrolled diabetes, ongoing or active infection, symptomatic congestive heart
failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, uncontrolled
arterial thrombosis, symptomatic pulmonary embolism, or psychiatric illness that would
limit compliance with study requirements, or any other conditions that would preclude
the patient from study treatment as per the discretion of the Investigator.
13. Significant cardiovascular history:
- History of myocardial infarction or ischemic heart disease within 1 year (within
a window of up to 18 days less than 1 year) before first study drug
administration;
- Uncontrolled arrhythmia;
- History of congenital QT prolongation;
- Electrocardiogram (ECG) findings consistent with active ischemic heart disease;
- New York Heart Association Class III or IV cardiac disease;
- Uncontrolled hypertension: blood pressure consistently >150 mm Hg systolic and >
100 mm Hg diastolic in spite of antihypertensive medication.
14. History of hemorrhagic diarrhea, inflammatory bowel disease, or active uncontrolled
peptic ulcer disease. (Concomitant therapy with ranitidine or its equivalent and/or
omeprazole or its equivalent is acceptable). History of ileus or other significant
gastrointestinal disorder known to predispose to ileus or chronic bowel hypomotility.
15. Any other malignancy requiring active therapy.
16. Known human immunodeficiency virus (HIV) seropositivity.
17. Active Hepatitis B virus (HBV) infection which requires antiviral treatment. Patients
with detectable Hepatitis B surface Antigen (HBsAg) may be eligible provided the
patient has a negative viral load. Patients with a positive HBsAg must have a negative
viral load before each chemotherapy administration. Hepatitis B surface antibody (anti
HBs) without detectable HBsAg does NOT exclude patients from the study. Hepatitis C
infection (Hepatitis C antibody reactive) which requires treatment also excludes
patients from the study.
18. Female subject who is pregnant or lactating.
19. Unwilling or unable to comply with procedures required in this protocol
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