TR64 in Patients With Advanced Solid Tumors

A Single-arm, Open-Label, Dose Escalation , Phase I Study to Evaluate the Safety, Tolerability and Pharmacokinetics of TR64 in Patients With Advanced Solid Tumors

This is a open-label, dose escalation, accelerated titration combined 3+3 design, phase I study, to evaluate the safety and tolerability, and to determine the RP2D of TR64 when administered qd in patients with advanced solid tumors. Up to 6 cohorts of 1-6 or 3-6 patients each will be treated in the study.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumor
• Intervention / Treatment: Drug: TR64

Detailed Description

Patients will receive study treatment until criteria for study termination are met. A Safety Follow-up Visit will be conducted 28 days (±7 days) after the last dose of study treatment. Patients who discontinue study treatment for reasons other disease progression will have post-treatment follow-up for disease assessment until start of new anticancer treatment, patient withdraws consent, is lost to follow-up, death, or until the Sponsor stops the study, whichever comes first.

Adverse events will be assessed using the NCI Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0.

Tumor response will be assessed by computed tomography (CT) and/or magnetic resonance imaging (MRI) scan using RECIST 1.1 criteria, assessed by the investigator.

• Study Type: Interventional
• Enrollment (Anticipated): 19
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Yang Shu, MD. BS.; Phone Number: 86-13918983465; Email: shuyang@tarapeutics.com

Study Locations

• China
  • Anhui
    • Bengbu, Anhui, China, 233004
      • Recruiting
      • The First Affiliated Hospital Of Bengbu Medical College
      • Contact: Huan Zhou, Ph.D; Phone Number: 13665527160; Email: zhouhuanbest@vip.163.com
  • Liaoning
    • Shenyang, Liaoning, China, 110002
      • Recruiting
      • The First Hospital of China Medical University
      • Contact: Funan Liu, MD Ph.D; Phone Number: 13609877906; Email: lfn_clinical@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Fully understand the procedures of the clinical study and participate voluntarily with signed and dated written informed consent form, comply with the requirements of the study protocol.
• Males and/or females at least 18 years old when signing the informed consent form.
• Histologically or cytologically confirmed patients with advanced malignant solid tumors, eligible patients must have failed standard treatment, no standard treatment, or not suitable for standard treatment at this stage as determined by the investigator.
• Measurable disease with at least one lesion amenable to response assessment per RECIST 1.1.
• Eastern cooperative oncology group performance status (ECOG) ≤2 at screening.
• Life expectancy of at least 3 months.
• Acceptable organ function: Absolute neutrophil count(ANC)≥1.5×109/L; Platelet count(PLT)≥90×109/L; Hemoglobin(Hb)≥90 g/L; Total bilirubin(TBIL)≤1.5×Upper limit of normal value(ULN); Alanine aminotransferase(ALT)≤2.5×ULN; Aspartate aminotransferase(AST)≤2.5×ULN; Creatinine clearance ≥50ml/min.
• Fertile male and female must agree to use medically approved contraceptives during the study and within 90 days after the last dose of the study.

Exclusion Criteria:

• Known or suspected allergies to any of the investigational drug composition.
• Medical history and surgical history excluded according to the protocol.
• Any previous medical treatment history exclude from the protocol.
• Abnormal laboratory results exclude from the protocol.
• pregnant and lactating women (currently breast-feeding or less than six months after delivery although not breast-feeding).
• Subjects may not be able to complete the study duo to poor compliance or other reasons, or unsuitable for the study by the investigator's judgment.

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: TR64; Daily doses by oral administration on each day of each 28 day cycle. Starting dose is 25mg, with escalation to 400mg, and subsequent dose escalation using a modified Fibonacci algorithm.	Drug: TR64; TR64 tablets will be given daily for 28 days in 28-day cycles until there appears evidence of progressive disease, intolerable toxicity, or the subject discontinues from the study treatment for other reasons.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events and Serious Adverse Events	Frequency, duration and severity of Adverse Events and Serious Adverse Events evaluated by NCI CTCAE v5.0	From the first dose to within 28 days after the last dose
Dose limited toxicities	Incidence of dose limited toxicities	within 28 days after the first dose
Maximum tolerated dose	Evaluated by safety review committee	Throughout the study for approximately 2 years
Recommended phaseII dose	Evaluated by safety review committee	Throughout the study for approximately 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUClast	Characterize the pharmacokinetic profile of TR64	within 35 days after the first dose
AUCinf	Characterize the pharmacokinetic profile of TR64	within 35 days after the first dose
Cmax	Characterize the pharmacokinetic profile of TR64	within 35 days after the first dose
Tmax	Characterize the pharmacokinetic profile of TR64	within 35 days after the first dose
CL/F	Characterize the pharmacokinetic profile of TR64	within 35 days after the first dose
Vz/F	Characterize the pharmacokinetic profile of TR64	within 35 days after the first dose
Terminal half-life (T1/2)	Characterize the pharmacokinetic profile of TR64	within 35 days after the first dose

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	Efficacy-Overall Response Rate	Throughout the study for approximately 2 years
PFS	Efficacy-Progression Free Survival	Throughout the study for approximately 2 years
DOR	Efficacy-Duration of Response	Throughout the study for approximately 2 years
CBR	Efficacy-Clinical Benefit Rate	Throughout the study for approximately 2 years

Collaborators and Investigators

• Sponsor: Tarapeutics Science Inc.
• Investigators: Principal Investigator: Huan Zhou, PhD, First Affiliated Hospital Bengbu Medical College; Principal Investigator: Funan Liu, MD, PhD, First Hospital of China Medical University

Study record dates

Study Major Dates

• Study Start (Actual): January 12, 2023
• Primary Completion (Anticipated): July 10, 2024
• Study Completion (Anticipated): January 10, 2025

Study Registration Dates

• First Submitted: November 22, 2022
• First Submitted That Met QC Criteria: December 5, 2022
• First Posted (Actual): December 14, 2022

Study Record Updates

• Last Update Posted (Actual): April 25, 2023
• Last Update Submitted That Met QC Criteria: April 23, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: TR64-CN-PI-01

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