Study of Intravenous TCD-717 in Patients With Advanced Solid Tumors

TCD Pharma has developed TCD-717, a novel drug that is a specific inhibitor of the enzyme
choline kinase alpha (ChoKα), involved in the synthesis of phosphatidylcholine, which
constitutes the major phospholipid in eukaryotic cell membranes and has been described as a
potent oncogen when overexpressed in human cells. TCD-717 will be evaluated in this Phase
I, open-label, single arm study to be performed at multiple centers. TCD-717 will be
administered as a 4 hour infusion on two separate days per 7-day period per 28-day cycle (8
administrations per cycle). Eligible patients must have confirmed, metastatic or
recurrent/refractory solid tumors.

Inclusion Criteria:

1. Patients must have histologically-confirmed solid tumors, metastatic or recurrent and
refractory after standard therapy for the disease or for which conventional therapy
is not reliably effective or no effective therapy is available.

2. Where possible, it is recommended that a paraffin block of tumor tissue or slides
containing sections of tumor tissue be available (a sample should be collected and
stored appropriately for the potential evaluation of choline kinase alpha expression
in tumor tissue at the end of the study).

3. Patients must be ≥ 18 years of age.

4. Patients must have an ECOG Performance Status of 0, 1 or 2 and an estimated life
expectancy of ≥ 12 weeks.

5. Patients must have adequate clinical laboratory values (i.e., absolute neutrophil
count ≥1.5x10^9/L, platelets ≥100x10^9/L, plasma creatinine <= 1.5 x upper limit of
normal (ULN) for the institution or a calculated creatinine clearance (using Cockroft
and Gault formula) of ≥ 60 mL/min/1.73 m^2; bilirubin < 1.5 x ULN, alanine
transaminase (ALT) and aspartate transaminase (AST) < 2.5 x ULN or ≤ 5 x ULN with
liver involvement.

6. Patients may have either measurable or non-measurable disease as defined by RECIST.

7. Patients must give signed informed consent prior to the start of any study specific
procedures.

8. Female patients with reproductive potential must have a negative serum or urine
pregnancy test.

9. Patients with reproductive potential and their partners must be using at least one
form of contraception as approved by the Investigator prior to study entry.

10. Patients with central nervous system metastases may be included if they are stable
without administration of steroids. Patients with unstable metastatic CNS disease
are excluded.

Exclusion Criteria:

1. Patients will be excluded if they have received previous anti-cancer chemotherapy,
immunotherapy, vaccines, monoclonal antibodies, anti-angiogenic therapy, radiotherapy
or any other investigational therapy within 4 weeks (6 weeks for nitrosoureas or
mitomycin C) prior to study entry. Patients receiving concurrent anticancer therapy
or intending to receive this at any time during the study will be excluded.

2. Patients who have received extensive prior radiotherapy to more than 30% of bone
marrow reserves, or prior bone marrow/stem cell transplantation at any time prior to
the study.

3. Patients with any concomitant condition that could compromise the objectives of this
study and the patient's compliance.

4. Patients with significant cardiac disease including heart failure that meets New York
Heart Association (NYHA) class III and IV definitions, history of myocardial
infarction within six months of study entry, uncontrolled dysrhythmias or poorly
controlled angina, uncontrolled hypertension or elevated heart rate.

5. Patients with a history of serious ventricular arrhythmia (VT or VF), QTc >=450 msec
for men and 470 msec for women (as indicated in the ECG taken in the pre-treatment
evaluation), or left ventricular ejection fraction (LVEF)<=50% by MUGA or
Echocardiogram performed at the pre-treatment evaluation.

6. Pregnant or lactating females.

7. Patients with clinically evident HIV, HBV or HCV infection.

8. Patients with a hematologic malignancy.

9. Patients with a documented or known bleeding disorder or who require anticoagulation
treatment that increases international normalized ratio (INR) or activated partial
thromboplastin time (aPTT) above the institutional upper limit of normal.

10. Patients with clinically significant retinal abnormalities as per the medical history
or ophthalmologic findings in the pre-treatment evaluation (e.g., retinitis
pigmentosa or macular degeneration).