A Phase I Study of the Safety, Tolerability, Pharmacokinetics Profile, and Preliminary Efficacy of TT-00434 in Patients With Advanced Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- TT-00434
- Conditions
- Advanced Solid Tumors
- Sponsor
- TransThera Sciences (Nanjing), Inc.
- Enrollment
- 11
- Locations
- 3
- Primary Endpoint
- Dose Limiting Toxicity (DLT)
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
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
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.
Investigators
Eligibility Criteria
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
- •(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.
Arms & Interventions
Dose Escalation
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.
Intervention: TT-00434
Outcomes
Primary Outcomes
Dose Limiting Toxicity (DLT)
Time Frame: At the end of Cycle 1 (each cycle is 28 days)
Safety and tolerability
Incidence of AEs
Time Frame: up to 30 days from study discontinuation
Safety and tolerability
Secondary Outcomes
- Time of first Occurance of Cmax（tmax)(At the end of Cycle 1 (each cycle is 28 days))
- Serum phosphate levels(up to 30 days from study discontinuation)
- Disease control rate (DCR)(through study completion, an average of 1 year)
- Peak Plasma Concentration (Cmax)(At the end of Cycle 1 (each cycle is 28 days))
- Overall Survival (OS)(through study completion, an average of 1 year)
- Area under the plasma concentration versus time curve (AUC)(At the end of Cycle 1 (each cycle is 28 days))
- Objective response rate (ORR)(through study completion, an average of 1 year)
- Progression Free Survival (PFS)(through study completion, an average of 1 year)