Phase I, First-in-human Study of Oral TP-1287 in Patients With Advanced Solid Tumors

Primary Objective:

- To determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of
oral TP-1287 in patients with advanced metastatic or progressive solid tumors who are
refractory to, or intolerant of, established therapy known to provide clinical benefit
for their condition.

- To establish the Recommended Phase 2 Dose (RP2D) for future studies with TP-1287

Secondary Objectives:

- To establish the pharmacokinetics of orally administered TP-1287

- To observe patients for any evidence of antitumor activity of TP-1287 by objective
radiographic assessment

- To study the pharmacodynamics of TP-1287 therapy

Inclusion Criteria:

1. Have a histologically confirmed diagnosis of advanced metastatic or progressive solid
tumor excluding tumor types with rapid cell turnover, ie, small cell cancer (lung and
extra pulmonary), inflammatory breast cancer (IBC), medulloblastoma, neuroblastoma and
melanoma with extensive liver metastasis (greater than or equal to 50% of the liver
involved; patients with melanoma and metastasis to less than 50% of the liver are
eligible)

2. Be refractory to, or intolerant of, established therapy known to provide clinical
benefit for their condition.

3. Have one or more tumors measurable or evaluable as outlined by modified Response
Evaluation Criteria in Solid Tumors (RECIST) v1.1

4. Have an Eastern Cooperative Oncology Group (ECOG) performance status of less than or
equal to 1

5. Have a life expectancy greater than or equal to 3 months

6. Be greater than or equal to 18 years of age

7. Have a negative pregnancy test (if female of childbearing potential)

8. Have acceptable liver function:

1. Bilirubin less than or equal to 1.5x upper limit of normal (ULN) (unless
attributed to Gilbert's syndrome)

2. Aspartate aminotransferase (AST/SGOT), alanine aminotransferase (ALT/SGPT) and
alkaline phosphatase less than or equal to 2.5x upper limit of normal (ULN) *If
liver metastases are present, then less than 3x ULN is allowed.

9. Have acceptable renal function:

a. Calculated creatinine clearance greater than or equal to 30 mL/min

10. Have acceptable hematologic status:

1. Granulocyte greater than or equal to 1500 cells/mm3

2. Platelet count greater than or equal to 100,000 (plt/mm3)

3. Hemoglobin greater than or equal to 8 g/dl

11. Have acceptable coagulation status:

1. Prothrombin time (PT) within 1.5x normal limits

2. Activated partial thromboplastin time (aPTT) within 1.5x normal limits

12. Be nonfertile or agree to use an adequate method of contraception. Sexually active
patients and their partners must use an effective method of contraception (hormonal or
barrier method of birth control; or abstinence) prior to study entry and for the
duration of study participation including for at least 3 months (males) and 6 months
(females) after the last dose of study drug. Should a woman become pregnant or suspect
she is pregnant while participating in this study, she should inform her treating
physician immediately.

13. Have read and signed the Institutional Review Board (IRB)-approved informed consent
form (ICF) prior to any study related procedure. (In the event that the patient is
re-screened for study participation or a protocol amendment alters the care of an
ongoing patient, a new ICF must be signed.)

Exclusion Criteria:

1. History of congestive heart failure (CHF), cardiac disease, myocardial infarction
within the past 6 months prior to Cycle 1 Day 1, left ventricular ejection fraction
(LVEF) less than 45% by echocardiogram (ECHO), unstable arrhythmia, or evidence of
ischemia on electrocardiogram (ECG) within 14 days prior to Cycle 1 Day 1

2. Have a corrected QT interval (using Fridericia's correction formula) (QTcF) of >450
msec in men and >470 msec in women

3. Have a seizure disorder requiring anticonvulsant therapy

4. Presence of symptomatic central nervous system metastatic disease or disease that
requires local therapy such as radiotherapy, surgery, or increasing dose of steroids
within the prior 2 weeks

5. Have severe chronic obstructive pulmonary disease with hypoxemia (defined as resting
02 saturation of less than or equal to 90% breathing room air)

6. Have undergone major surgery within 2 weeks prior to Cycle 1 Day 1

7. Have active, uncontrolled bacterial, viral, or fungal infections, requiring systemic
therapy

8. Are pregnant or nursing

9. Received treatment with radiation therapy, surgery, chemotherapy, or investigational
therapy within 28 days or 5 half-lives, whichever occurs first, prior to study entry
(6 weeks for nitrosoureas or Mitomycin C)

10. Are unwilling or unable to comply with procedures required in this protocol

11. Have known infection with human immunodeficiency virus (HIV), hepatitis B, or
hepatitis C. Patients with history of chronic hepatitis that is currently not active
are eligible.

12. Have a serious nonmalignant disease (e.g., hydronephrosis, liver failure, or other
conditions) that could compromise protocol objectives in the opinion of the
investigator and/or the sponsor

13. Are currently receiving any other investigational agent

14. Have exhibited allergic reactions to a similar structural compound, biological agent,
or formulation

15. Have malabsorption conditions (eg, Crohn's disease, etc) or Have undergone significant
surgery to the gastrointestinal tract that could impair absorption or that could
result in short bowel syndrome with diarrhea due to malabsorption