Dose-escalation Study of Intravenous Liposomal Vinorelbine Tartrate Injection in Patients With Advanced Malignancy

Protocol No: TLC178A1001

Name of Finished Product: LipoVNB (Liposomal Vinorelbine Tartrate)

Title of Study:

Phase I/IIa, Open label, Dose-escalation Study Investigating the Safety, Tolerability, and
Pharmacokinetics of Intravenous Liposomal Vinorelbine Tartrate Injection in Patients with
Advanced Malignancy.

Study duration:

Every patient will have a treatment period of 4-week cycles until completion of 6 cycles,
progression of disease or intolerance, withdrawal of consent or Investigator's judgment,
whichever occurs first.

Inclusion Criteria:

1. Male or female, ≥18 years of age (≥20 years of age in Taiwan)

2. Patients with histologically/cytologically confirmed solid tumor, or lymphoma. For the
expansion cohort, only patients with peripheral/cutaneous T cell lymphoma, Hodgkin's
lymphoma, and other non-Hodgkin's lymphoma would be considered eligible

3. Malignancies for which there is no standard therapy, or previously treated locally
advanced, refractory/relapsed or metastatic disease for which local curative surgery,
curable radiotherapy, or satisfactory systemic anticancer therapy is no longer
available

4. Assessable disease status defined by Cheson (for lymphoma) or modified severity
weighted assessment tool (mSWAT) (for mycosis fungoides [MF] and Sezary syndrome [SS])
criteria, or having measurable tumors defined by Response Evaluation Criteria in Solid
Tumors guidelines (RECIST 1.1) (for solid tumor)

5. Eastern Collaborative Oncology Group (ECOG) Performance Status of ≤2

6. Anticipated life expectancy of more than 3 months per Investigator's judgement

7. Women of childbearing potential must have a negative urine pregnancy test at the
screening visit

8. Male patients with female partners of childbearing potential, and female patients of
childbearing potential must agree to use effective birth control. Effective birth
control and cessation of lactation must be complied at least 2 weeks prior to first
study drug administration, during the trial participation, and for 3 months after the
last dose of study drug

9. Willing and able to comply with the study procedure and sign a written informed
consent

Exclusion Criteria:

1. Patient with untreated or inadequate controlled brain metastases. Brain metastases or
lymphoma with CNS involvement previously treated by radiotherapy or other modality and
stable for at least 3 months prior to screening without requirement of corticosteroids
or anticonvulsants are permitted

2. Prior systemic standard or investigational anticancer therapy, including target
therapy, chemotherapy, immunotherapy within 28 days prior to the first dose of study
drug. The above mentioned conditions which the Investigator considers there is no more
drug effect, such as ≥5 half-lives are permitted

3. More than 5 lines of previous cytotoxic therapies. For patients of CTCL who failed
romidepsin, more than 4 lines of previous therapies

4. Extensive prior radiotherapy on more than 30% of bone marrow reserves or prior bone
marrow/stem cell transplantation within 2 years before screening. Limited field
radiation for ≤2 weeks prior to screening period is permitted

5. Any toxicity due to prior therapy that has not been resolved to less than Grade 2
severity by Common Terminology Criteria for Adverse Events (CTCAE, Version 4.03 or
higher) criteria

6. Medical history of uncontrolled but clinically significant abnormal cardiac conduction
abnormalities at electrocardiogram (ECG), any history or evidence of long QT syndrome
or QTcF interval >450 msec for males and ≥470 msec for females (according to
Fridericia's correction) at screening

7. Poor vital organ function defined as:

- Absolute neutrophil count (ANC) <1,500/mm3, pre-transfusion platelets
<100,000/mm3, or pre-transfusion hemoglobin <9.0 mg/dL (the patient is required
to have at least 2 weeks free from blood transfusion, G-CSF and erythropoietin
use prior to the hematology test)

- International Normalized Ratio (INR) for coagulation above upper normal range

- Total bilirubin >1.5 times upper limit of normal (ULN)

- Aspartate amino transferase (AST) or Alanine amino transferase (ALT) >3 times ULN
in patient without liver metastasis or liver cirrhosis

- Child Pugh B or C stage liver disease

- Creatinine clearance (by Cockcroft Gault formula) <40 mL/min

8. Use of potent inhibitors or inducers of cytochrome P450 enzymes CYP3A4 within 14 days
prior to first study drug administration.