A Phase 1 study of FF-10850, topotecan liposome injection, in advanced solid tumors including ovarian and cervical carcinomas, sarcomas, and neuroendocrine tumors including small cell lung cancer and Merkel cell carcinoma

To determine the safety profile, maximum tolerated dose (MTD), dose-limiting toxicities
(DLTs), and recommended Phase 2 dose (RP2D) of FF-10850 (topotecan liposome injection) in
patients with 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