This is a study to investigate the absorption, metabolism and excretion of [14C] labeled
ASP8273 in subjects with solid tumors harboring EGFR mutations (per local testing). This
study consists of two parts (A and B).
This study consists of two parts (A and B).
In Part A, eligible subjects will be admitted to the site on day -1 and remain confined at
the site until postdosing discharge criteria are met. Subjects will receive a single dose of
[14C] ASP8273 solution on study day 1.
Once Part A has been completed, subjects may elect to continue participation in Part B.
Subjects will receive oral administration of ASP8273 (nonradiolabeled) once daily in 28-day
- Subject has histologically or cytologically confirmed metastatic or locally advanced,
unresectable solid tumors harboring EGFR mutations.
- Subject has Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
- Subject must meet all of the following criteria on the laboratory tests that will be
performed within 7 days prior to enrollment. In case of multiple laboratory data
within this period, the most recent data should be used.
- Neutrophil count ≥ 1,000/mm3
- Platelet count ≥ 7.5 × 104/mm3
- Hemoglobin ≥ 9.0 g/dL
- Lymphocyte count ≥ 500/mm3
- Estimated glomerular filtration rate (eGFR) of > 50 ml/min as calculated by the
- Total bilirubin (TBL) < 1.5 × upper limit of normal (ULN; except for subjects
with documented Gilbert's syndrome)
- Aspartate aminotransferase (AST) and ALT < 3.0 × ULN
- Serum sodium level is ≥ 130 mmol/L
- Female subject must either be:
- Of nonchild bearing potential:
1. Postmenopausal (defined as at least 1 year without any menses) prior to
2. Documented surgically sterile or status post hysterectomy (at least 1 month
prior to screening).
- Or, if of childbearing potential:
1. Agree not to try to become pregnant during the study and for 28 days after
the final study drug administration,
2. Must have a negative serum pregnancy test at screening and day -1, and
3. If heterosexually active must use two forms of birth control* (at least one
of which must be a barrier method) starting at screening and throughout the
study period and for 28 days after the final study drug administration.
- Female subject must not be breastfeeding at screening or during the study period, and
for 28 days after the final study drug administration.
- Female subject must not donate ova starting at screening and throughout the study
period, and for 28 days after the final study drug administration.
- Male subject and his female spouse/partner who is of childbearing potential must be
using highly effective contraception consisting of two forms of birth control* (one of
which must be a barrier method) starting at screening and continue throughout the
study period and for 90 days after the final study drug administration.
- Male subject must not donate sperm starting at screening and throughout the study
period and for 90 days after the final study drug administration.
*Acceptable forms of birth control include:
- Established use of oral, injected or implanted hormonal methods of contraception.
- Placement of an intrauterine device (IUD) or intrauterine system (IUS).
- Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault
caps) with spermicidal foam/gel/film/cream/suppository.
- Subject has an ongoing toxicity ≥ Grade 2 (Common Terminology Criteria for Adverse
Event [CTCAE] v4.03) attributable to prior medication to treat solid tumor (except
alopecia) at the time of screening.
- Subject has known history of serious hypersensitivity reaction to ASP8273, or any
component of the formulation used.
- Subject has received investigational therapy within 28 days or 5 half-lives, whichever
is shorter, prior to the first dose of study drug.
- Subject has received a prior EGFR inhibitor within 6 days prior to the first dose of
- Subject has had any of the following within 14 days prior to the first dose of study
- A treatment with any other agent with antitumor activity including chemotherapy,
radiotherapy, or immunotherapy
- A major surgical procedure (other than study related biopsy), or a major surgical
is planned to occur during the study
- Blood transfusions or hemopoietic factor therapy
- Evidence of active infection requiring systemic therapy
- Subject has symptomatic central nervous system (CNS) metastasis. Subject with
previously treated brain or CNS metastases are eligible provided that the subject has
recovered from any acute effects of radiotherapy and is not requiring steroids, and
any whole brain radiation therapy was completed at least 2 weeks prior to study drug
administration, or any stereotactic radiosurgery (SRS) was completed at least 1 week
prior the first dose of study drug.
- Subject has ≥ CTCAE v4.03 Grade 2 neuropathy.
- Subject has a known history of a positive test for hepatitis B surface antigen (HBsAg)
or hepatitis C antibody (anti-HCV).
- Subject has a known history of a positive test for human immunodeficiency virus (HIV)
- Subject has history of drug-induced interstitial lung disease (ILD) or any evidence of
- Subject has severe or uncontrolled systemic diseases including uncontrolled
hypertension (blood pressure > 150/100 mmHg) or active bleeding diatheses.
- Subject has ongoing cardiac arrhythmia that is Grade ≥ 2 or uncontrolled atrial
fibrillation of any grade.
- Subject currently has Class 3 or 4 New York Heart Association congestive heart
- Subject has history of severe/unstable angina, myocardial infarction, or
cerebrovascular accident within 6 months prior to the first dose of study drug.
- Subject has concurrent corneal disorder or any ophthalmologic condition which, in the
Investigator's opinion, makes the subject unsuitable for study participation (e.g.,
advanced cataracts, glaucoma, or subject is unable to undergo a comprehensive
- Subject has history of gastrointestinal ulcer or gastrointestinal bleeding within 3
months prior to the first dose of study drug.
- Subject has difficulty taking oral medication or any digestive tract dysfunction or
inflammatory bowel disease that would interfere with the intestinal absorption of
- Subject who has received strong/moderate inhibitors or inducers of CYP3A4 within 14
days prior to the first dose of study drug.