A Japanese Phase 1 Trial of TH-302 in Subjects With Solid Tumors and Pancreatic Cancer

A Japanese Single Center, Open-label, Phase I Trial of TH-302 Given Intravenously to Subjects With Solid Tumors as Monotherapy or to Subjects With Advanced Pancreatic Cancer in Combination With Gemcitabine

This is a Japanese Phase 1, open-label, and dose-escalating trial of TH-302 as monotherapy in subjects with solid tumors and in combination with gemcitabine in subjects with pancreatic cancer.

Inclusion Criteria:

• At least 20 years of age
• Signed written informed consent form
• Histologically or cytologically confirmed advanced or metastatic solid tumor previously treated with one or more standard treatment regimen(s) or for which no effective therapy is available
• Histologically or cytologically confirmed locally advanced unresectable or metastatic pancreatic adenocarcinoma previously untreated with chemotherapy or systemic therapy
• Recovered from toxicities of prior anti-cancer treatment to Grade 1 or less
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Life expectancy of at least 3 months
• Acceptable liver function, renal function, hematologic status and coagulation status as defined in the protocol
• No clinically significant abnormalities in urinalysis
• Effective contraception for both male and female subjects if the risk of conception exists
• Other inclusion criteria apply

Exclusion Criteria:

• Prior anti-cancer treatment with more than 3 myelosuppressive cytotoxic chemotherapy regimens
• Prior treatment with gemcitabine for their advanced or metastatic pancreatic cancer, except for radiosensitizing doses of gemcitabine
• Prior radiotherapy to more than 30 percent of the bone marrow within 6 months prior to the trial entry
• Cardiac disease with New York Heart Association (NYHA) Class 3 or 4, within 6 months prior to the trial entry
• Clinically significant (that is, active) cardiovascular disease
• Seizure disorders requiring anticonvulsant therapy
• Known brain, leptomeningeal or epidural metastases (unless previously treated and well controlled for at least 3 months at the trial entry)
• Previously treated malignancies other than the current disease for at least 5 years at the trial entry
• Severe chronic obstructive or other pulmonary disease major surgery, within 4 weeks prior to the trial entry, without complete recovery
• Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy
• Anti-cancer treatment prior to trial entry
• Participation in an investigational drug or device trial within 4 weeks prior to the trial entry
• Known infection with human immunodeficiency virus (HIV), Hepatitis B, or Hepatitis C
• A history of allergic reactions
• Taking a medication that is either moderate or strong inhibitor or inducer of cytochrome P450 (CYP)3A4 or is a sensitive substrate of other cytochrome P450
• Pregnancy or lactation period
• Concomitant disease or condition that could interfere with the conduct of the trial, or that would, in the opinion of the Investigator, pose an unacceptable risk to the subject in this trial
• Unwillingness or inability to comply with the trial protocol for any reason
• Legal incapacity or limited legal capacity
• Other exclusion criteria apply