Study of the of the Safety and Tolerability of TT-00434 in Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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This is a phase I study of the safety, tolerability, pharmacokinetics profile, and preliminary efficacy of TT-00434 in patients with advanced solid tumors.

Detailed Description
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This is a phase I, First-in-Human (FIH), open-label, dose escalation clinical study in patients who have a histological or cytologically confirmed diagnosis of advanced or recurrent tumors that all standard treatments have been used or are not feasible. It aims to determine the maximum tolerated dose (MTD) and/or the recommended phase 2 dose (RP2D) for study, evaluate the safety, tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) characteristics and the preliminary anti-tumor activity of TT-00434, and explore the relationship between the anti-tumor activity of TT-00434 and the tumor FGFR alterations.

Official Title
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A Phase I Study of the Safety, Tolerability, Pharmacokinetics Profile, and Preliminary Efficacy of TT-00434 in Patients With Advanced Solid Tumors

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Drug: TT-00434


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 20 years. Patients must have a histological or cytologically confirmed diagnosis of advanced or recurrent malignant solid tumors. Patients have received all currently available standard treatments (unless the therapy is contraindicated, intolerable or unavailable due to any reasons). Patients must have measurable or evaluable disease (according to RECIST 1.1) Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2 Must agree to take sufficient contraceptive methods to avoid pregnancy during the study and until at least 6 months after ceasing study treatment Patients must have fully understood and voluntarily signed informed consent form (ICF) for this study. Exclusion Criteria: Patients who received other investigational products or devices in other clinical trials within 4 weeks before the first dose. Patients who received anti-tumor therapy within 4 weeks, or within 5-half-lives (which is longer) before the first dose, including but not limited to chemotherapy, radiotherapy (palliative radiotherapy is completed at least 2 weeks before the first dose can enrol), targeted therapy or immunotherapy. Patients who have previous toxicity of anti-tumor therapy that has not recovered to Grade 1. (except for ≤ Grade 2 alopecia, chemotherapy-induced peripheral neurotoxicity, and ototoxicity). Patients who have gastrointestinal disorders that will affect oral administration or the Investigator judges that the absorption of TT-00434 will be interfered. Patients underwent major surgery (except biopsy) within 4 weeks, or the surgical incision has not completely healed prior to the first dose. Patients who have active bacterial or fungal infections (CTCAE, Grade ≥ 2) that required systemic treatment within 2 weeks prior to the first dose. Patients who have active HBV infection (HBV DNA copies ≥ ULN) and/or HCV infection (HCV RNA copies ≥ ULN) Patients who test positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome. Has received a live-virus vaccination within 30 days of planned first dose NOTE: Seasonal flu vaccines are permitted. Known or suspected drug hypersensitivity to any ingredients of TT-00434 tablets. Female patients in pregnancy or lactation. Male patients or female patients at reproductive ages who are unwilling to receive effective contraceptive measures. Patients who are judged by the Investigator to be unsuitable for this study.

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Escalation<br>This study adopts an accelerated titration design (ATD) and utilizes an accelerated dose escalation phase in order to minimize suboptimal drug exposures, followed by a conventional 3+3 dose escalation phase to achieve MTD. | Drug: TT-00434<br>* Once daily [QD], 28 days/cycle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose Limiting Toxicity (DLT) | Safety and tolerability | At the end of Cycle 1 (each cycle is 28 days) | 
| Incidence of AEs | Safety and tolerability | up to 30 days from study discontinuation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak Plasma Concentration (Cmax) | PK evaluation | At the end of Cycle 1 (each cycle is 28 days) | 
| Area under the plasma concentration versus time curve (AUC) | PK evaluation | At the end of Cycle 1 (each cycle is 28 days) | 
| Time of first Occurance of Cmax（tmax) | PK evaluation | At the end of Cycle 1 (each cycle is 28 days) | 
| Serum phosphate levels | PD biomarker | up to 30 days from study discontinuation | 
| Objective response rate (ORR) | Assess anti-tumor activity | through study completion, an average of 1 year | 
| Disease control rate (DCR) | Assess anti-tumor activity | through study completion, an average of 1 year | 
| Progression Free Survival (PFS) | Assess anti-tumor activity | through study completion, an average of 1 year | 
| Overall Survival (OS) | Assess anti-tumor activity | through study completion, an average of 1 year |