Safety Study of IHL-305 (Irinotecan Liposome Injection) to Treat Advanced Solid Tumors

This is a Phase I dose-escalation study of intravenous administration of IHL-305 in patients
with advanced solid tumors. Patients will receive IHL-305 as an intravenous infusion over 60
minutes on Day 1 followed by a 27-day observation period for a total of 28 days (4 weeks)
per cycle. Two patient populations will be evaluated separately; patients with UGT1A1*28
genotype homozygous wild-type (wt/wt) and heterozygous (wt/*28) variants as one group, and
patients with UGT1A1*28 homozygous variant (*28/*28) as another group.

Inclusion Criteria:

1. Histologically confirmed malignant solid tumor and not a candidate for known regimens
or protocol treatments of higher efficacy or priority

2. Failed conventional therapy for their cancer or have a malignancy for which a
conventional therapy does not exist

3. Recovered from all acute adverse effects of prior therapies, excluding alopecia (hair
loss)

4. ECOG performance status of 0, 1, or 2

5. 18 years of age or older

6. Normal organ and bone marrow function as defined by:

- absolute neutrophil count greater than or equal to 1,500 cells/microliter

- platelets greater than or equal to 100,000 cells/microliter

- total bilirubin within normal institutional limits

- AST (SGOT)/ALT (SGPT) less than or equal to 2.5 x institutional upper limit of
normal (ULN) or less than or equal to 5.0 x ULN in patients with liver
metastases

- plasma creatinine less than or equal to 1.5 x institutional ULN OR

- creatinine clearance greater than or equal to 60 mL/min/1.73 m2 for patients
with creatinine levels above institutional normal

7. Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

1. Previously treated with irinotecan, or had chemotherapy or radiotherapy within 4
weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study, or not
recovered from adverse effects due to agents administered more than 4 weeks earlier

2. Receiving any other investigational agent

3. Known brain metastases

4. History of allergic reactions attributed to compounds of similar chemical composition
to IHL-305

5. Concurrent serious infections (i.e., requiring an intravenous antibiotic)

6. Pregnant women or women of childbearing potential and not using methods to avoid
pregnancy; a negative pregnancy test (urine or serum) must be documented at baseline
for women of childbearing potential; no breast-feeding while on study.

7. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, unstable angina pectoris, or psychiatric illness/social situations that
would limit compliance with study requirements

8. Significant cardiac disease including heart failure that meets New York Heart
Association (NYHA) class III and IV definitions; history of myocardial infarction
within one year of study entry; uncontrolled dysrhythmias; or poorly controlled
angina.

9. History of serious ventricular arrhythmia (ventricular tachycardia [VT] or
ventricular fibrillation [VF], greater than or equal to 3 beats in a row); QTc
greater than or equal to 450 msec for men and 470 msec for women; or left ventricular
ejection fraction (LVEF) less than or equal to 40% by multi-gated acquisition scan
(MUGA).