Phase 1 Study of Oral TP-1454
Study Details
Study Description
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 |
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Phase 1 |
Detailed Description
Primary Objectives During Dose Escalation:
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To establish the MTD and/or Recommended Phase 2 Dose (RP2D) of orally administered TP-1454 monotherapy in patients with advanced metastatic solid tumors
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To establish the MTD and/or RP2D of orally administered TP-1454 in combination with ipilimumab and nivolumab in patients with advanced/ metastatic renal cell carcinoma (RCC) and patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC), who are eligible per FDA approval of ipilimumab and nivolumab by indication for the protocol- defined regimen
Secondary Objectives During Dose Escalation:
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To establish the pharmacokinetic (PK) profile of orally administered TP-1454 alone and in combination with ipilimumab and nivolumab
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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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To assess the safety and tolerability of oral TP-1454 administered as monotherapy and in combination with ipilimumab and nivolumab in the defined patient populations
Primary Objectives During Dose Expansion:
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To evaluate the preliminary antitumor activity, by objective radiographic assessment, of TP-1454 in combination with ipilimumab and nivolumab in patients with mNSCLC expressing PD-L1 (≥1% as determined by an FDA-approved test) with no EGFR or ALK genomic tumor aberrations
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To establish the RP2D of orally administered TP-1454 in combination with ipilimumab and nivolumab in the defined patient population
Secondary Objectives During Dose Expansion:
• To assess the safety and tolerability of oral TP-1454 in combination with ipilimumab and nivolumab in the defined patient population
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Monotherapy TP-1454 |
Drug: TP-1454 monotherapy
Flat dose once or twice daily, alone
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Experimental: Combination Therapy TP-1454, ipilimumab and nivolumab |
Drug: TP-1454 combination therapy
Flat dose once or twice daily, in combination with ipilimumab and nivolumab
|
Outcome Measures
Primary Outcome Measures
- During Dose Escalation: Incidence of dose-limiting toxicities (DLTs) [21 or 28 days]
A DLT is defined as a drug-related toxicity that is observed to occur within the first 21 or 28 days of treatment depending on which arm the patient is enrolled in (monotherapy 28 days; combination 21 days).
- During Dose Escalation: Determine maximum tolerated dose (MTD) [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.
- During Dose Escalation: Recommended Ph 2 dose of TP-1454 [28 months]
To establish the recommended Ph 2 dose (RP2D) for future studies with TP-1454. MTD, PK and PD data to be reviewed.
- During Dose Expansion: Determine the preliminary antitumor activity of TP-1454 in combination with ipilimumab and nivolumab [18 months]
Determine the preliminary antitumor activity of TP-1454 in combination with ipilimumab and nivolumab in terms of objective response rate (ORR) in patients with mNSCLC expressing PD-L1 (≥1% as determined by an FDA-approved test) with no EGFR or ALK genomic tumor aberrations according to RECIST v 1.1 and iRECIST.
- During Dose Expansion: Recommended Ph 2 dose of TP-1454 in combination with ipilimumab and nivolumab [18 months]
Establish the Recommended Ph2 dose for future studies of orally administered TP-1454 in combination with ipilimumab and nivolumab in the defined population. MTD, PK and PD data will be reviewed.
Secondary Outcome Measures
- During Dose Escalation: Determine antitumor activity of TP-1454. [28 months]
Objective radiographic assessment to be performed to determine antitumor activity by Response Evaluation Criteria in Solid Tumors (RECIST criteria v 1.1.
- During Dose Expansion: Asses the safety and tolerability of TP-1454 [18 months]
Assess the safety and tolerability of oral TP-1454 in combination with ipilimumab and nivolumab in the defined patient population. MTD, PK and PD data will be reviewed.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Dose Escalation: Have a histologically confirmed diagnosis of a) advanced metastatic or progressive solid tumor, who are refractory to, or intolerant of, established therapy known to provide clinical benefit for their condition (Monotherapy Arm) b) advanced/metastatic renal cell carcinoma (RCC) and patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC), who are eligible per FDA approval of ipilimumab and nivolumab by indication for the protocol- defined regimen (combination arm).
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Dose Expansion: Have a histologically confirmed diagnosis of mNSCLC expressing PD-L1 (≥1% as determined by an FDA-approved test) with no EGFR or ALK genomic tumor aberrations, and who are eligible per FDA approval of ipilimumab and nivolumab by indication for the protocol-defined regimen
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Naïve to prior treatment with any PD1 or CTLA-4 inhibitor (Combination Arm Only)
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Have measurable as outlined by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
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Have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤1
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Have a life expectancy ≥3 months
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Be ≥18 years of age
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Have a negative pregnancy test (if female of childbearing potential)
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Have acceptable liver function:
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Bilirubin ≤1.5x upper limit of normal (ULN) (unless associated with Gilbert syndrome)
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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
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Have acceptable renal function: calculated creatinine clearance ≥30 mL/min (using Cockcroft Gault formula)
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Have acceptable hematologic status:
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Granulocyte ≥1500 cells/mm3
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Platelet count ≥100,000 (plt/mm3)
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Hemoglobin ≥8 g/dL
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Have acceptable coagulation status:
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Prothrombin time (PT) within 1.5x normal limits
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Activated partial thromboplastin time (aPTT) within 1.5x normal limits
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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.
- 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:
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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
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Have a corrected QT interval (using Fridericia's correction formula) (QTcF) of >450 msec in men and >470 msec in women
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Have a seizure disorder requiring anticonvulsant therapy
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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
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Have hypoxemia (defined as resting O2 saturation of ≤90% breathing room air)
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Have symptomatic interstitial lung disease or radiographic changes in the lungs that may make detection, diagnosis, or treatment of drug-induced pneumonitis difficult
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Have undergone major surgery within 2 weeks prior to Cycle 1/Day 1
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Have active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy
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Are pregnant or nursing
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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)
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Are unwilling or unable to comply with procedures required in this protocol
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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
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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
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Are currently receiving any other investigational agent
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Have exhibited allergic reactions to a similar structural compound, biological agent, or formulation
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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
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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) (patients receiving combination therapy only)
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Have a history of malignancy within the past 24 months except curatively treated in situ cancers
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Have active, known, or suspected autoimmune disease with the exception of (patients receiving combination therapy only):
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Type I diabetes mellitus
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Hypothyroidism only requiring hormone replacement
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Skin disorders not requiring systemic treatment, eg, vitiligo, alopecia, or psoriasis
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Have known EGFR mutations or ALK alterations that are sensitive to targeted therapy in NSCLC tumor types (patients receiving combination therapy only)
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Have ≥Grade 2 peripheral neuropathy (patients receiving combination therapy only)
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Mayo Clinic Arizona | Phoenix | Arizona | United States | 85054 |
2 | University of Southern California - Norris Cancer Center and Hoag Memorial Hospital | Los Angeles | California | United States | 90033 and 92663 |
3 | Mayo Clinic Jacksonville | Jacksonville | Florida | United States | 32224 |
4 | Mayo Clinic Rochester | Rochester | Minnesota | United States | 55905 |
5 | Comprehensive Cancer Center of Nevada | Las Vegas | Nevada | United States | 89169 |
6 | Texas Oncology Baylor Sammons Cancer Center | Dallas | Texas | United States | 75246 |
7 | Huntsman Cancer Institute | Salt Lake City | Utah | United States | 84112 |
8 | University of Virginia | Charlottesville | Virginia | United States | 22908 |
9 | Medical College of Wisconsin | Milwaukee | Wisconsin | United States | 53226 |
Sponsors and Collaborators
- Sumitomo Pharma Oncology, Inc.
Investigators
- Study Director: Gregory Pennock, MD, Sumitomo Pharma Oncology, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- TP-1454-101