Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.
Inclusion Criteria:
1. Patients to be enrolled during Dose Escalation with capsules must have a histologically confirmed diagnosis of advanced metastatic or progressive solid tumor who are refractory to, or intolerant of, established therapy known to provide clinical benefit for their condition (enrollment complete).
2. Following approval of Amendment 5, patients to be enrolled during Dose Escalation with Tablets must have a histologically confirmed diagnosis of metastatic squamous cell carcinoma of the anus (mSCCA) and:
1. have received at least one line of systemic platinum-based therapy in the advanced setting;
(Note: Systemic platinum therapy given in the adjuvant setting will meet this criterion if there is recurrence or metastasis within 6 months of
completing adjuvant therapy.); and
2. have received no more than 3 total lines of systemic therapy in the advanced setting.
3. Have measurable disease 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. Be ≥ 18 years of age.
6. Have a negative pregnancy test (if female of childbearing potential).
7. Have acceptable liver function:
1. Bilirubin ≤ 1. 5 x upper limit of normal (ULN) (unless associated with Gilbert syndrome)
2. Aspartate aminotransferase (AST/SGOT), alanine aminotransferase (ALT/SGPT) and alkaline phosphatase ≤ 2.5 x ULN* *If liver metastases are present, then ≤ 3 x ULN
is allowed.
*If liver metastases are present, then 3x ULN is allowed.
8. Have acceptable renal function: calculated creatinine clearance ≥30 mL/min (using Cockcroft Gault formula)
9. Have acceptable hematologic status:
1. Granulocyte ≥ 1500 cells/mm^3
2. Platelet count ≥ 100,000 (plt/mm^3)
3. Hemoglobin ≥ 8 g/dL
10. Have acceptable coagulation status:
1. Patient has International Normalized Ratio (INR) or Prothrombin time (PT) ≤ 1.5 × ULN unless the patient is receiving anticoagulant therapy, in which case, the patient’s PT or partial thromboplastin time (PTT) must be within the therapeutic range of intended use for their anticoagulant;
2. Patient has PTT or activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless the patient is receiving anticoagulant therapy, in which case, the patient’s PT or PTT must be within the therapeutic range of intended use for their anticoagulant.
11. 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 for the duration of study participation and for at least 3 months (males) and 6 months (females) after the last study drug dose.
12. Male patients only: must agree not to donate sperm during the study and for 3 months after the last dose of TP-1454.
13. Women of childbearing potential must agree not to donate eggs during the study and for 6 months after the last dose of TP-1454.
14. 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).
15. Dose escalation in mSCCA with tablets only: Patients who are HIV+ may be enrolled if the following conditions are met:
1. CD4+ T-cell count ≥ 300/µL;
2. No opportunistic infection within the past 12 months;
3. Treatment with established antiretroviral therapy for at least 4 weeks with a viral load < 400 copies/mL prior to first dose with TP-1454.
16. Dose escalation in mSCCA with tablets only: Patients who have had hepatitis B or C viral infections (HBV or HCV, respectively) may be enrolled if the following conditions are met:
1. Have completed or are undergoing curative antiviral treatment with viral load below the limit of quantification;
2. Test positive for antibody and negative for viral RNA.
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 > 470 msec.
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 ≥ 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.
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 to a target lesion, 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. Dose escalation in solid tumors with capsules only: Have known infection with hepatitis B, or hepatitis C. Patients with history of chronic hepatitis that is currently not active are eligible.
13. 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.
14. Are currently receiving any other investigational agent.
15. Have exhibited allergic reactions to a similar structural compound, biological agent, or formulation(s).
16. Have malabsorption conditions (e.g., Crohn’s disease) 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. Have a history of malignancy within the past 24 months except curatively treated in situ cancers
Note: Other protocol defined Inclusion/Exclusion Criteria may apply.
Eligibility last updated 11/29/23. Questions regarding updates should be directed to the study team contact.