ACY 241 in Combination With Paclitaxel in Patients With Advanced Solid Tumors

Patients will receive ACY 241 with dose escalation according to a 3 + 3 design in combination
with paclitaxel at the dose and schedule used in clinical practice for the patient population
treated in this protocol.

Patients will undergo screening assessments for protocol eligibility within 28 days of study
start (Cycle 1 Day 1).

Patients will receive ACY 241 by oral administration once daily (QD) or, if supported by PK
and safety data, twice daily on 21 consecutive days of a 28 day treatment cycle. Paclitaxel
will be administered to patients at 80 mg/m2 IV over 1 hour on Days 1, 8, and 15 of the 28
day treatment cycle. Patients who experience a DLT or other unacceptable toxicity in Cycle 1
will be removed from study treatment. Patients will receive study treatment until documented
progressive disease (PD) or unacceptable toxicity.

Each cohort will consist of at least 3 patients. Patients who withdraw consent in Cycle 1
will be replaced. An assessment of safety will be made by the Safety Review Committee (SRC)
before dose escalation. The SRC will be composed of the Study Investigators, the Sponsor's
Medical Monitor and Clinical Project Lead, and the Contract Research Organization's Safety
Monitor, Project Manager, and Biometrician. Ad hoc members may be invited by the Sponsor as
needed.

Inclusion Criteria:

1. Must be able to understand and voluntarily sign an informed consent form (ICF).

2. Must be ≥ 18 years of age at the time of signing the ICF.

3. Must be able to adhere to the study visit schedule and other protocol requirements.

4. Patients must have a histologically confirmed nonhematological, metastatic or locally
advanced, incurable malignancy for which paclitaxel is clinically appropriate.
Patients must have received and failed standard treatment for their malignancy;
patients for whom no standard treatment is available will also be eligible.

5. Evaluable disease by Response Evaluation Criteria in Solid Tumors (RECIST) version
1.1.

6. Life expectancy > 12 weeks.

7. Must have Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1,
or 2.

8. Patients with the potential for pregnancy or impregnating their partner must agree to
follow acceptable birth control methods to avoid conception. Females of childbearing
potential must have a negative pregnancy test. It is not known if the antideacetylase
activity of this experimental drug may be harmful to the developing fetus or nursing
infant.

Exclusion Criteria:

1. Any serious medical condition, laboratory abnormality, or psychiatric illness that
would prevent the patient from giving informed consent.

2. Any serious concurrent medical conditions, laboratory abnormality, or psychiatric
illness that might make the patient nonevaluable, put the patient's safety at risk, or
prevent the patient from following the study requirements.

3. Pregnant or lactating females.

4. Patients with uncontrolled brain metastases.

5. Patients who have had chemotherapy or radiotherapy within 2 weeks (6 weeks for
nitrosoureas or mitomycin C) before entering the study or those who have not recovered
from AEs to ≤ Grade 1 (except for peripheral neuropathy; see Exclusion Criterion 12)
due to agents administered more than 4 weeks earlier.

6. Previous therapy with histone deacetylase (HDAC) inhibitor.

7. Any of the following laboratory abnormalities:

- ANC < 1,500/µL.

- Platelet count < 100,000/µL

- Hematologic growth factors are not allowed at Screening or during the first cycle
of treatment.

- Hemoglobin < 9 g/dL (< 5.5 mmol/L; previous red blood cell [RBC] transfusion is
permitted).

- Creatinine > 1.5 × upper limit of normal (ULN).

- AST or ALT > 2.5 × ULN. For patients with liver metastasis AST or ALT > 5 × ULN.

- Serum total bilirubin > 1.5 mg/dL or > 3 × ULN for patients with hereditary
benign hyperbilirubinemia

8. Corrected QT interval (QTc) using Fridericia's formula (QTcF) value > 480 msec at
Screening; family or personal history of long QTc syndrome or ventricular arrhythmias
including ventricular bigeminy at Screening; previous history of drug induced QTc
prolongation or the need for treatment with medications known or suspected of
producing prolonged QTc intervals on electrocardiogram (ECG).

9. Congestive heart failure (New York Heart Association Class III or IV), myocardial
infarction within 12 months before starting study treatment, or unstable or poorly
controlled angina pectoris, including Prinzmetal variant angina pectoris.

10. Positive human immunodeficiency virus, hepatitis B virus, and hepatitis C virus
infection.

11. Hypersensitivity to taxanes (such as Steven Johnson syndrome). Hypersensitivity, such
as rash < Grade 3 that is managed, is allowed.

12. Peripheral neuropathy > Grade 2 despite supportive therapy.

13. Patients who received any of the following within the 14 days before initiating study
treatment:

- Major surgery

- Radiation therapy

- Systemic therapy (standard or an investigational or biological anticancer agent)

14. Current enrollment in another clinical study involving treatment and/or is receiving
an investigational agent for any reason, or use of any investigational agents within
28 days or 5 half lives (whichever is longer) of initiating study treatment.

15. Incidence of gastrointestinal disease that may significantly alter the absorption of
ACY 241.