A Study of FF-10850 Topotecan Liposome Injection in Advanced Solid Tumors

Inclusion Criteria:

Patients must meet all the following criteria to participate in the study:

1. Males and females ≥ 18 years of age
2. Dose-escalation phase: Histologically or cytologically confirmed metastatic and/or unresectable solid tumor, relapsed or refractory to standard therapy, or for which no standard therapy is available that is expected to improve survival by at least 3 months
3. At least 3 weeks beyond the last chemotherapy (or 3 half-lives, whichever is shorter), radiotherapy, major surgery, or experimental treatment, and recovered from all acute toxicities (≤ Grade 1), prior to the first dose of FF-10850
4. Adequate performance status: Eastern Cooperative Oncology Group (ECOG) ≤ 1
5. Life expectancy of ≥ 3 months

6. Adequate hematologic parameters without ongoing transfusion support:

   • Hemoglobin (Hb) ≥ 9 g/dL
   • Absolute neutrophil count (ANC) ≥ 1.0 × 109 cells/L
   • Platelets ≥ 100 × 109 cells/L
7. Creatinine ≤ 1.5 × ULN, or calculated creatinine clearance ≥ 50 mL/minute by either the Cockcroft-Gault formula or as measured by a 24-hour urine collection
8. Total bilirubin ≤ 2 × ULN unless due to Gilbert's disease; patients with Gilbert's disease who have a total bilirubin > 6 mg/dL are to be excluded
9. ALT and AST ≤ 2.5 times ULN, or < 5 × ULN for patients with liver metastases
10. QT interval corrected for rate (QT interval corrected for rate using Fridericia's Correction Formula, QTcF) ≤ 470 msec for women and ≤ 450 msec for men on the ECG obtained at Screening and confirmed pre-treatment on Cycle 1 Day 1.
11. Patient must be willing to undergo a tumor biopsy, if the patient has a biopsy-accessible tumor

Exclusion Criteria:

1. Patients who have not received standard/approved therapies expected to improve survival by at least 3 months
2. History of severe hypersensitivity reactions to topotecan
3. Serious cardiac condition within the last 6 months, such as uncontrolled arrhythmia, myocardial infarction, unstable angina or heart disease defined by the New York Heart Association (NYHA) Class III or Class IV or hereditary long QT syndrome
4. Concomitant medication(s) that may cause QTc prolongation or induce Torsades de Pointes, except for antimicrobials that are used as standard of care to prevent or treat infections and other such drugs that are considered by the Investigator to be essential for patient care
5. Active central nervous system (CNS) malignant disease in patients with a history of CNS malignancy. Patients with previously treated stable brain metastases are allowed if they have been stable off steroid therapy for at least 4 weeks.
6. Known positive for human immunodeficiency virus (HIV), hepatitis B virus surface antigen (HBsAg) or hepatitis C virus (HCV)
7. Active infection requiring intravenous (IV) antibiotic usage within the last week prior to study treatment
8. Any other medical intervention or other condition which, in the opinion of the Principal Investigator, could compromise adherence to study requirements or confound the interpretation of study results
9. Pregnant or breast-feeding