Vosaroxin for Intermediate 2 or High-risk MDS After Failure With Hypomethylating Agent-based Therapy

This is a phase 1-2, dose escalation study of the safety and clinical activity of vosaroxin
in subjects with INT-2 or high risk MDS who have failed prior hypomethylating agent based
therapy. The study will utilize a standard 3+3 design to estimate the MTD [maximum tolerated
dose] for vosaroxin administered to subjects with MDS. MTD will be defined as the highest
dose level at which no more than 33% of the subjects observed at a given dose level
experience a DLT [dose limiting toxicity]. Subjects will be assessed for safety and DLT in
the first cycle of vosaroxin. Subjects will be enrolled into the study in cohorts of 3. Three
eligible subjects will be enrolled in sequential cohorts at increasing dose levels until at
least 1 DLT is observed during the first cycle of vosaroxin therapy. Subjects who receive
both doses of vosaroxin will be evaluated for the MTD, DLTs, and safety profile during the
first cycle of therapy. Once the MTD has been determined, an expanded evaluation of safety
and hematologic response or improvement rate at this dose level will be conducted in
additional subjects so that the total number of subjects exposed to this dose level is up to
15 subjects, inclusive of those treated at this dose level in the dose-escalation phase. The
exposure of additional subjects at the MTD will provide a better estimate of the toxicity
rate. Subjects with a documented response of Complete Response, Partial Response, or
hematologic improvement at the end of Cycle 2 may continue to receive vosaroxin for
additional cycles at the discretion of the treating investigator and after discussion with
the medical staff at Sunesis Pharmaceuticals. There will be a 30-day follow-up period
following the termination of study drug treatment.

Inclusion Criteria:

- Able to understand and to provide written informed consent

- At least 18 years of age with pathologically confirmed MDS (< 20% blasts in bone
marrow, peripheral blood, or both) by WHO classification with an intermediate 2 or
high-risk score assessed by IPSS (score ≥ 1.5)

- Must have received at least 4 cycles of decitabine-based or 6 cycles of
azacitidine-based therapy and are either refractory to, relapsed after, or are
intolerant of prior therapy with either agent.

1. Primary failure/refractory: Stable or worsening disease after a minimum of 4
cycles of decitabine-based or 6 cycles of azacitidine-based therapy

2. Secondary failure/relapse: Bone marrow blast count increase or loss of
hematologic response after initial treatment response with hypomethylating
agent-based therapy

3. Intolerance: Intolerance of hypomethylating agent-based therapy regardless of
number of cycles completed and clinical response

- Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0-2

- Must have a life expectancy of at least 2 months

- Must demonstrate adequate clinical laboratory values (based on local laboratory
results) as follows:

1. Serum creatinine 1.5 ≤ x the upper limit of normal (ULN) or calculated creatinine
clearance (CLCR) of ≥ 50 mL/min

2. Total bilirubin ≤ 1.5 x ULN, higher levels are acceptable if these can be
attributed to active hemolysis (as indicated by positive Coomb's test, decreased
haptoglobin, Gilbert's disease, elevated indirect bilirubin, and/or lactate
dehydrogenase) or ineffective erythropoiesis (as indicated by bone marrow
findings).

3. Aspartate aminotransferase (AST) ≤ 2.5 x ULN

4. Alanine aminotransferase (ALT) ≤ 2.5 x ULN

5. Must show adequate cardiac function defined as a left ventricular ejection
fraction (LVEF)

- 40% by echocardiogram (ECHO) or multigated acquisition (MUGA) scan

- Must have acceptable recovery from clinically significant non-hematologic toxicity
after prior therapy

- Must be infertile or agree to use an effective contraceptive method for the duration
of the study and for 30 days after the last dose (for men and women of child-producing
potential).

Exclusion Criteria:

- Patients meeting any of the following criteria are excluded:

- Presence of AML (≥ 20% blasts in bone marrow, peripheral blood, or both)

- Presence of serious illness, medical condition, or other medical history, involving
the heart, kidney, liver or other organ system, including abnormal laboratory
parameters, which, in the opinion of the Investigator, would be likely to interfere
with a subject's participation in the study or with the interpretation of the results.

- Have known active central nervous system disease or active, uncontrolled, clinically
significant infection(s).

- Have other active malignancies (including other hematologic malignancies) or other
malignancies within 12 months before enrollment, except nonmelanoma skin cancer or
cervical intraepithelial neoplasia

- Have experienced CTCAE Grade 2 or greater oral mucositis within the last 14 days

- Are receiving any other investigational therapy or protocol-prohibited therapy

- Have received previous treatment with vosaroxin

- Pregnant or breastfeeding females

- Known allergy to D-sorbitol or methanesulfonic acid (excipients used in vosaroxin)

- Treatment with any anticancer therapy (including radiation) within the previous 14
days prior to the first dose of study drug or less than full recovery (CTCAE grade 1)
from the clinically significant toxic effects of that treatment.

- Treatment with any investigational drugs within the previous 14 days prior to Cycle 1,
Day 1 or ongoing adverse events from previous cancer treatment with investigational
drugs, regardless of the time period.

- Have any other medical, psychological, or social condition that, in the opinion of the
PI, would contraindicate the patient's participation in the clinical study due to
safety or compliance with clinical study procedures