A Study of TBI-1401(HF10) in Patients With Solid Tumors With Superficial Lesions

This is an open label, non-randomized, dose escalation Phase I study evaluating the repeated intratumoral administrations of the TBI-1401(HF10), a spontaneously attenuated mutant of HSV-1, in patients with solid tumors with superficial lesions (e.g., malignant melanoma and squamous cell carcinoma of the skin).

The study will evaluate the safety and tolerability of repeated intratumoral administrations of TBI-1401(HF10) at dose levels of 1 x 10^6 TCID50/dose (cohort 1) and 1 x 10^7 TCID50/dose (cohort 2) in Japanese patients. Three patients will be enrolled in each cohort. Patients in the each cohort will receive a total of four intratumoral administrations in the same lesion.

Inclusion criteria

• Patients must have histologically confirmed solid tumors with superficial lesions.
• Patients must have unresectable and standard therapies-resistant solid tumors.
• Patients must be ≥ 20 years of age.
• Patients must have a life expectancy ≥ 12 weeks.
• Patients must have measurable non-visceral lesion(s) that are evaluable by the mWHO response criteria.
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
• Patients must have adequate key organ function (bone marrow, heart, lung, liver, renal, etc), as defined as

• Absolute neutrophil count ≥ 1,500/μL.
• Platelet count ≥ 100,000/μL.
• Total bilirubin levels ≤ 1.5 x upper limit of normal (ULN).
• AST/ALT levels ≤ 2.5 x ULN, or ≤ 5 x ULN if liver metastases are present.
• creatinine ≤ 1.5 x ULN.
• creatinine clearance (calculated) ≥ 60 mL/min/1.73 m^2 for patients with creatinine > 1.5 x ULN.
• Patients must have passed 4 weeks after the completion of prior therapy [except bone metastasis therapy], or passed 8 weeks if immuno checkpoint inhibitor was treated.
• Patients must be able to understand and willing to sign a written informed consent document.

Exclusion criteria

• Patients with a history of significant tumor bleeding, or coagulation or bleeding disorders.
• Patients with Grade 2 adverse events Grade 2 or greater, except alopecia, resulting from anticancer agents administered more than 4 weeks prior to TBI-1401(HF10) administration.
• Patients receiving anti-herpes medication [except local treatment such as ointment].
• Patients receiving steroids or immunosuppressive agents [except inhaled steroid].
• Patients with clinically evident Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV) or Hepatitis C virus (HCV) infection.
• Patients receiving anti-platelet medication.
• Patients receiving anti-coagulation medication.
• Patients with presence or medical history of central nervous system metastasis.
• Patients with Grade ≥ 2 pre-existing neurologic abnormalities (CTCAE version 4.0).
• Patients with severe cardiac disorder or abnormal cardiac rhythm.
• Patients with psychiatric disorder or drug dependency which affects informed consent.
• Pregnant or breastfeeding women; women or men, having normal reproductive potential, who disagree with the protection of pregnancy within the timeframe of the study.
• Patients received any other investigational products within 4 weeks, or within 8 weeks if immuno checkpoint inhibitor was treated.
• Patients would limit compliance with study requirements, as determined by the investigator.