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

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

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

Study Overview

• Status: Completed
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: TT-00434

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.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Jia Wang; Phone Number: 8602558216298; Email: wangjia@transtherabio.com

Study Locations

• Taiwan
  • Tainan, Taiwan
    • National Cheng Kung University Hospital
  • Taipei, Taiwan
    • Tri-Service General Hospital
  • Taipei, Taiwan
    • Taipei Medical University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: TT-00434; Once daily [QD], 28 days/cycle.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: TransThera Sciences (Nanjing), Inc.
• Investigators: Principal Investigator: Huey En Tzeng, Taipei Medical University Hospital; Principal Investigator: Chia Jui Yen, National Cheng-Kung University Hospital; Principal Investigator: Ching Liang Ho, Tri-Service General Hospital; Principal Investigator: Ming Che Liu, Taipei Medical University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 12, 2021
• Primary Completion (Actual): October 18, 2023
• Study Completion (Actual): October 18, 2023

Study Registration Dates

• First Submitted: March 28, 2021
• First Submitted That Met QC Criteria: April 1, 2021
• First Posted (Actual): April 5, 2021

Study Record Updates

• Last Update Posted (Actual): November 21, 2023
• Last Update Submitted That Met QC Criteria: November 20, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: TT00434CN01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No