Phase 1 Study of Oral TP-1454

• Status: Recruiting
• Trial end date: 2022-12-01
• Target enrollment: 0
• Participant gender: All

Summary

This study will evaluate the safety and tolerability of oral TP-1454 in patients with advanced metastatic or progressive solid tumors, alone and in combination with Ipilimumab and Nivolumab.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Sumitomo Dainippon Pharma Oncology, Inc; Tolero Pharmaceuticals, Inc.
• Treatments: Ipilimumab; Nivolumab

Criteria

Inclusion Criteria:

1. Have a histologically confirmed diagnosis of advanced metastatic or progressive solid tumor,

1. who are refractory to, or intolerant of, established therapy known to provide clinical benefit for their condition (Monotherapy Arm)

2. who the investigator deems appropriate for treatment with the defined regimen of ipilimumab and nivolumab (Combination Arm).

2. Naïve to prior treatment with any PD1 or CTLA-4 inhibitor (Combination Arm Only)

3. Have measurable as outlined by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

4. Have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤1

5. Have a life expectancy ≥3 months

6. Be ≥18 years of age

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

8. Have acceptable liver function:

1. Bilirubin ≤1.5x upper limit of normal (ULN) (unless associated with Gilbert syndrome)

2. Aspartate aminotransferase (AST/SGOT), alanine aminotransferase (ALT/SGPT) and alkaline phosphatase ≤2.5x ULN* *If liver metastases are present, then ≤ 3x ULN is allowed. ** For patients who will receive ipilimumab and nivolumab in combination with TP-1454 then ≤ 3X ULN is allowed

9. Have acceptable renal function: calculated creatinine clearance ≥30 mL/min (using Cockcroft Gault formula)

10. Have acceptable hematologic status:

1. Granulocyte ≥1500 cells/mm3

2. Platelet count ≥100,000 (plt/mm3)

3. Hemoglobin ≥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 and for at least 3 months (males) and 6 months (females) after the last study drug dose.

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 rescreened for study participation or a protocol amendment alters the care of an ongoing patient, a new ICF must be signed.)

Exclusion Criteria:

1. New York Heart Association Class III or IV cardiac disease, or myocardial infarction, severe unstable angina, coronary/peripheral artery bypass graft, congestive heart failure within the past 6 months 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. Have untreated central nervous system (CNS) metastases including carcinomatous meningitis. Patients with definitively treated (radiotherapy or surgery) CNS metastases may be eligible if asymptomatic and not receiving corticosteroids in excess of prednisone 10 mg (or equivalent) per day for ≥2 weeks before first dose of TP-1454

5. Have hypoxemia (defined as resting O2 saturation of ≤90% breathing room air)

6. Have symptomatic interstitial lung disease or radiographic changes in the lungs that may make detection, diagnosis, or treatment of drug-induced pneumonitis difficult

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

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

9. Are pregnant or nursing

10. 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)

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

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

13. Have a serious nonmalignant disease (eg, hydronephrosis, liver failure, or other conditions) that could compromise protocol objectives in the opinion of the Investigator and/or the Sponsor

14. Are currently receiving any other investigational agent

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

16. 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

17. Require systemic corticosteroids greater than the equivalent of 10mg of prednisone or equivalent alternative steroid (except physiologic dose for adrenal replacement therapy) or other immunosuppressive agents (e.g., cyclosporine or methotrexate)

18. Have a history of malignancy within the past 24 months except curatively treated in situ cancers

19. Have active, known, or suspected autoimmune disease with the exception of (combination arm only):

• Type I diabetes mellitus

• Hypothyroidism only requiring hormone replacement

• Skin disorders not requiring systemic treatment, eg, vitiligo, alopecia, or psoriasis

20. Have known EGFR mutations or ALK alterations that are sensitive to targeted therapy in NSCLC tumor types (combination arm only)

21. Have ≥Grade 2 peripheral neuropathy (combination arm only)