Phase 1, First-in-human Study of Oral TP-1287 in Patients with Advanced Solid Tumors

Inclusion Criteria

• •1. For Dose Escalation:
• •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.
• •2. For Dose Expansion:
• •1. Patients who have histologically confirmed locally advanced or metastatic unresectable Ewing sarcoma
• •2. Have received at least one prior line of treatment (but no more than 5 prior lines) including an anthracycline.
• •3. Have one or more measurable 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 at the time of informed consent/assent.
• •6. Be greater than or equal to 18 years of age for dose escalation and expansion; Patients with Ewing sarcoma aged ≥ 12 years may also participate in dose expansion if they weigh ≥40 kg
• •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 or equal to 5x ULN is allowed.
• •* If bone metastases are present, but bilirubin, AST, ALT are ≤2.5x ULN, then there is no upper limit for alkaline phosphatase level. Radiographic proof of bone involvement is required, and alkaline phosphatase fractionation is strongly recommended to confirm the elevation is due to bony metastases.
• •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 a highly effective method of contraception 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. Male patients must agree not to donate sperm during the study and for 3 months after the last dose of TP-1287 due to unknown risks and potential harm to an unborn child/infant.
• •14. Female patients must agree not to donate eggs during the study and for 6 months after the last dose of TP-1287 due to unknown risks and potential harm to an unborn child/infant.
• •15. 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.) Assent is also required for patients who have not attained the legal age of consent for treatments or procedures involved in research.