Clinical Trials /

Phase 1 Study of Oral TP-1454

NCT04328740

Description:

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.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Phase 1 Study of Oral TP-1454
  • Official Title: A Phase I, First-in-human, Open-label, Dose Escalation, Safety, Pharmacokinetic, and Pharmacodynamic Study of Oral TP 1454 Alone and in Combination With Ipilimumab and Nivolumab

Clinical Trial IDs

  • ORG STUDY ID: TP-1454-101
  • NCT ID: NCT04328740

Conditions

  • Advanced Solid Tumor

Interventions

DrugSynonymsArms
TP-1454 monotherapyMonotherapy
TP-1454 combination therapyCombination Therapy

Purpose

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.

Detailed Description

      Primary Objective:

        -  To establish the safety of oral TP-1454 administered once daily in patients with
           advanced metastatic or progressive solid tumors a monotherapy and in patients who are
           eligible for standard of care treatment with ipilimumab and nivolumab as combination
           therapy

        -  To establish the dose of TP-1454 recommended to be used alone and in combination with
           ipilimumab and nivolumab in future studies for selected advanced solid tumors

      Secondary Objectives:

        -  To establish the pharmacokinetic (PK) profile of orally administered TP-1454 alone and
           in combination with ipilimumab and nivolumab

        -  To observe patients for any evidence of antitumor activity of TP 1454 alone and in
           combination with ipilimumab and nivolumab by objective radiographic assessment
    

Trial Arms

NameTypeDescriptionInterventions
MonotherapyExperimentalTP-1454
  • TP-1454 monotherapy
Combination TherapyExperimentalTP-1454, ipilimumab and nivolumab
  • TP-1454 combination therapy

Eligibility 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. that are eligible for standard of care treatment with ipilimumab and nivolumab
                  according to the Prescribing Information in the Label (Combination Arm).

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

          3. Have one or more tumors 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

         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. Contraindications to ipilimumab or nivolumab treatment (Combination Arm only)

          2. 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

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

          4. Have a seizure disorder requiring anticonvulsant therapy

          5. 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

          6. Have severe chronic obstructive pulmonary disease with hypoxemia (defined as resting
             O2 saturation of ≤90% breathing room air)

          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. Contraindications to an FDG PET Scan

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

         13. 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

         14. 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

         15. Are currently receiving any other investigational agent

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

         17. 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

         18. 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)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of dose-limiting toxicities (DLTs)
Time Frame:28 months
Safety Issue:
Description:A DLT is defined as a drug-related toxicity that is observed to occur within the first 28 days of treatment.

Secondary Outcome Measures

Measure:Determine antitumor activity of TP-1454.
Time Frame:28 months
Safety Issue:
Description:Objective radiographic assessment to be performed to determine antitumor activity by Response Evaluation Criteria in Solid Tumors (RECIST criteria v 1.1.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Tolero Pharmaceuticals, Inc.

Trial Keywords

  • Tolero Advanced Solid Tumors
  • Phase 1
  • Advanced Solid Tumors
  • Refractory

Last Updated

March 29, 2020