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Phase 1 Study of Oral TP-1454

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04328740
Recruitment Status : Not yet recruiting
First Posted : March 31, 2020
Last Update Posted : July 10, 2020
Sponsor:
Information provided by (Responsible Party):
Sumitomo Dainippon Pharma Oncology, Inc

Brief 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.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumor Drug: TP-1454 monotherapy Drug: TP-1454 combination therapy Phase 1

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 44 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Open label
Masking: None (Open Label)
Primary Purpose: Treatment
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
Estimated Study Start Date : July 2020
Estimated Primary Completion Date : November 2022
Estimated Study Completion Date : December 2022

Arm Intervention/treatment
Experimental: Monotherapy
TP-1454
Drug: TP-1454 monotherapy
Flat dose once daily, alone

Experimental: Combination Therapy
TP-1454, ipilimumab and nivolumab
Drug: TP-1454 combination therapy
Flat dose once daily, in combination with ipilimumab and nivolumab




Primary Outcome Measures :
  1. Incidence of dose-limiting toxicities (DLTs) [ Time Frame: 28 months ]
    A DLT is defined as a drug-related toxicity that is observed to occur within the first 28 days of treatment.

  2. Determine maximum tolerated dose (MTD) [ Time Frame: 28 months ]
    MTD will be determined based upon toxicity grades which are defined by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v 5.0.

  3. Recommended Ph 2 dose of TP-1454 [ Time Frame: 28 months ]
    To establish the recommended Ph 2 dose (RP2D) for future studies with TP-1454. MTD data to be reviewed.


Secondary Outcome Measures :
  1. Determine antitumor activity of TP-1454. [ Time Frame: 28 months ]
    Objective radiographic assessment to be performed to determine antitumor activity by Response Evaluation Criteria in Solid Tumors (RECIST criteria v 1.1.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04328740


Contacts
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Contact: Holly Beever, RN 210-365-9014 hbeever@toleropharma.com
Contact: Susan Smith, MSN 210-414-7702

Locations
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United States, Nevada
Comprehensive Cancer Center of Nevada
Las Vegas, Nevada, United States, 89169
Contact: Nicholas Vogelzang, MD         
Principal Investigator: Nicholas Vogelzang, MD         
Sponsors and Collaborators
Sumitomo Dainippon Pharma Oncology, Inc
Investigators
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Study Director: Stephen Anthony, DO Sumitomo Dainippon Pharma Oncology, Inc
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Responsible Party: Sumitomo Dainippon Pharma Oncology, Inc
ClinicalTrials.gov Identifier: NCT04328740    
Other Study ID Numbers: TP-1454-101
First Posted: March 31, 2020    Key Record Dates
Last Update Posted: July 10, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Sumitomo Dainippon Pharma Oncology, Inc:
Tolero Advanced Solid Tumors
Phase 1
Advanced Solid Tumors
Refractory