A Phase 1, Dose Escalation Study to Assess the Safety and Tolerability of ASP9853 With Either Docetaxel or Paclitaxel in Patients With Advanced Non-hematologic Malignancies

A Phase 1, Multicenter, Open-Label, Dose Escalation Study of ASP9853 in Combination With Either Docetaxel or Paclitaxel in Subjects With Advanced Non-hematologic Malignancies

The purpose of this study is to determine the safety and tolerability and pharmacokinetics of ASP9853 combined with docetaxel or with paclitaxel in subjects with advanced non-hematologic malignancies.

This is a two part study. Part 1 will test increasing dose levels of ASP9853 in combination with docetaxel. Part 2 will test increasing doses of ASP9853 combined with paclitaxel. Each part will determine the maximum tolerated dose and recommended Phase 2 dose for ASP9853 in combination with each taxane. Preliminary evidence of antitumor activity of ASP9853 in combination with docetaxel or with paclitaxel also will be explored.

Inclusion Criteria:

• Subject must have a histologically or cytologically confirmed incurable, locally advanced, or metastatic non-hematologic malignancy that has progressed or failed to respond to regimens or therapies known to provide clinical benefit
• Subject must have an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
• Subject must have recovered from the effects of prior systemic antineoplastic or radiation therapy(s) to ≤ Grade 1 severity or to subject's baseline values, excluding alopecia
• Subject agrees not to participate in another interventional study while on treatment

Female subject must be either:

Of non child bearing potential:

• post-menopausal (defined as at least 1 year without any menses) prior to Screening or
• documented surgically sterile or status post hysterectomy (at least 1 month prior to Screening)

Or, if of childbearing potential:

• must have a negative serum pregnancy test at Screening and
• 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 final study drug administration

Acceptable forms 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
• Female subject must not donate ova starting at Screening and throughout the study period and for 28 days after final study drug administration.
• Male subject must not donate sperm starting at Screening and throughout the study period and for 28 days after final study drug administration.
• Subject with adequate bone marrow, renal, and hepatic function at baseline

Exclusion Criteria:

• Subject has received more than 3 prior cytotoxic agent-containing regimens

• Subjects with prior anaphylactic or hypersensitivity reaction to prior taxane therapy

• Subject with symptomatic central nervous system (CNS) metastases or leptomeningeal involvement

• Subjects who received treatments with any of the following:

  • Systemic chemotherapy within 21 days
  • Nitrosoureas or mitomycin C within 42 days
  • Radiotherapy to ≥ 25% of hematopoietically active bone marrow within 21 days

• Subject had major surgical procedure within 28 days or anticipates need for major surgical procedure during course of the study

• Female subjects who are breastfeeding at Screening or during the study period and for 28 days after final study drug administration.

• Subject with peripheral neuropathy > Grade 1 at baseline

• Subject with known hepatitis B surface antigen (HBsAg) positive status; or known or suspected active hepatitis C infection; or known human immunodeficiency virus (HIV) positive

• Subject with malabsorption syndrome or disease or condition significantly affecting gastrointestinal function

• Subject with significant or uncontrolled cardiac, renal, hepatic or other systemic disorders, or significant psychological conditions at baseline

• Subject with clinically significant electrocardiogram (ECG) abnormalities on 12 lead ECG performed within 14 days before start of study drug

• Subject who has received strong inhibitors or inducers of CYP3A4 within two weeks prior to start of study treatment and while on study

• Subject has participated in any interventional clinical study or has been treated with any investigational drugs within 30 days or 5 half lives, whichever is longer, prior to the initiation of Screening