A Study to Evaluate the Tolerance, Efficacy and Pharmacokinetics of TQB3558 Tablets

A Phase I, Open-label, Dose Escalation and Expansion Study to Evaluate the Tolerance, Efficacy and Pharmacokinetics of TQB3558 Tablets

This is a study to evaluate the maximum tolerated dose (MTD) , occurrence of all adverse events (AE) and serious adverse events (SAE) , pharmacokinetic parameters and antitumor effect of TQB3558 tablets in Chinese adult patients with advanced solid tumors .The study is divided into phase Ia and phase Ib. Phase Ia: dose escalation period, to evaluate the safety and tolerability of TQB3558 tablets, determine MTD; Phase Ib: effectiveness exploration period, to expand the safe and effective dose group, recommend appropriate dosage and method for subsequent clinical research.

Study Overview

• Status: Unknown
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: TQB3558

• Study Type: Interventional
• Enrollment (Anticipated): 70
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200233
      • Recruiting
      • Shanghai Sixth People's Hospital
      • Contact: Zan Shen, Doctor; Phone Number: 021-24058431; Email: Sshenzzan@vip.sina.com
      • Principal Investigator: Zan Shen, Doctor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 1. Histologically or cytologically confirmed advanced malignant solid tumors, without conventional treatment methods or fail or relapse after treatment.

  2. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1; Life expectancy ≥12 weeks.

  3. Has at least one measurable lesion (based on RECIST 1.1) or bone metastases. 4. Adequate organ system function. 5. Patients need to adopt effective methods of contraception. 6. Understood and signed an informed consent form.

Exclusion Criteria:

• 1. Has received TRK inhibitors. 2. Has participated in any other clinical trials, or used other anti-cancer drugs, or received major surgical operations within 4 weeks before first administration.

  3. Has received local radiotherapy within 7 days or bone marrow radiotherapy within 4 weeks before the first administration.

  4. Has other malignant tumors in 2 years, except for cured or locally curable cancers.

  5. Has known spinal cord compression and cancerous meningitis. 6. Has interstitial lung disease, drug-induced interstitial lung disease, history of radiation lung disease requiring steroid therapy.

  7. Uncontrollable pleural effusion, pericardial effusion or ascites requiring repeated drainage.

  8. Obvious cardiovascular diseases. 9. Has a history of autoimmune disease, immunodeficiency. 10. Lactating women. 11. According to the judgement of the researchers, there are other factors that subjects are not suitable for the 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: TQB3558 Tablets; TQB3558 tablets administered orally once. Then TQB3558 tablet administered orally, once daily in 28-day cycle after 4 days of first administration.	Drug: TQB3558; TQB3558 is a kinase inhibitor of the TRK protein family.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum tolerated dose (MTD)	MTD was defined as the dose in which more than 2 of up to 6 patients developed a DLT.	Baseline up to 28 days
Adverse events (AE) and serious adverse events (SAE)	The occurrence of all adverse events (AE) and serious adverse events (SAE).	Baseline up to 28 days
Overall response rate (ORR)	Percentage of participants achieving complete response (CR) and partial response (PR).	up to 96 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tmax	To characterize the pharmacokinetics of TQB3558 by assessment of time to reach maximum plasma concentration.	15minutes, 30minutes, 1hour, 2hour, 4hour, 6hour, 8hour,10hour, 24hour, 48hour post-dose on day 1 and day 11; 30minutes pre-dose on day 1, day 5, day 7,day 8 ,day 9 and day 11.
Cmax	Cmax is the maximum plasma concentration of TQB3558 or metabolite(s).	15minutes, 30minutes, 1hour, 2hour, 4hour, 6hour, 8hour,10hour, 24hour, 48hour post-dose on day 1 and day 11; 30minutes pre-dose on day 1, day 5, day 7,day 8 ,day 9 and day 11.
AUC0-t	To characterize the pharmacokinetics of TQB3558 by assessment of area under the plasma concentration time curve from zero to infinity.	15minutes, 30minutes, 1hour, 2hour, 4hour, 6hour, 8hour,10hour, 24hour, 48hour post-dose on day 1 and day 11; 30minutes pre-dose on day 1, day 5, day 7,day 8 ,day 9 and day 11.
CL/f	CL/f is total clearance rate for TQB3558.	15minutes, 30minutes, 1hour, 2hour, 4hour, 6hour, 8hour,10hour, 24hour, 48hour post-dose on day 1 and day 11; 30minutes pre-dose on day 1, day 5, day 7,day 8 ,day 9 and day 11.
Disease control rate（DCR）	Percentage of participants achieving Complete Response (CR) and Partial Response (PR) and Stable Disease (SD).	up to 96 weeks
Progression-free survival (PFS)	PFS defined as the time from first dose to the first documented progressive disease (PD) or death from any cause.	up to 96 weeks
Duration of Response (DOR)	DOR defined as time from earliest date of disease response to earliest date of disease progression based on radiographic assessment.	up to 96 weeks

Collaborators and Investigators

• Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): June 25, 2020
• Primary Completion (Anticipated): July 31, 2022
• Study Completion (Anticipated): October 31, 2022

Study Registration Dates

• First Submitted: May 26, 2020
• First Submitted That Met QC Criteria: May 26, 2020
• First Posted (Actual): May 29, 2020

Study Record Updates

• Last Update Posted (Actual): July 8, 2020
• Last Update Submitted That Met QC Criteria: July 6, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Other Study ID Numbers: TQB3558-Ⅰ-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No