A Study to Evaluate the Tolerance, Efficacy and Pharmacokinetics of TQB3454 Tablets

A Phase I, Open-label, Dose Escalation and Expansion Study to Evaluate the Tolerance, Efficacy and Pharmacokinetics of TQB3454 Tablets

This is a open-label, multicenter, phase I study to evaluate tolerance and pharmacokinetics of TQB3454 tablets in subjects with advanced solid tumor or hematologic tumor.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumor or Hematologic Tumor
• Intervention / Treatment: Drug: TQB3454

• Study Type: Interventional
• Enrollment (Anticipated): 96
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100089
      • Recruiting
      • Beijing Cancer Hospital
  • Jiangsu
    • Xuzhou, Jiangsu, China, 221000
      • Recruiting
      • The Affiliated Hosptial Of XuZhou Medical University
      • Contact: Kailin Xu, doctor; Phone Number: 0516-85609999; Email: lihmd@163.com
  • Tianjin
    • Tianjin, Tianjin, China, 300020
      • Recruiting
      • Tianjing Medical University Cancer Institute&Hospital
      • Contact: Yi Ba, Doctor; Phone Number: 022-23909999; Email: bayi@tjmuch.com
      • Contact: Yafei Wang; Phone Number: 022-23909999; Email: Drwang2005@163.com
    • Tianjin, Tianjin, China, 300041
      • Recruiting
      • Hematology Hospital of Chinese Academy of Medical Sciences
  • Zhejiang
    • Hangzhou, Zhejiang, China, 311100
      • Recruiting
      • The First Affiliated Hosptial Zhejiang University School of Medical
      • Contact: Yi Zheng, Doctor; Phone Number: 0571-87235114; Email: oncologist@zju.edu.cn
      • Contact: Jian Liu, Master; Phone Number: 0571-87235114; Email: lindaliu87@zju.edu.cn

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

2. Advanced solid tumors or hematological malignancy. 3. Adequate laboratory indicators. 4. No pregnant or breastfeeding women, and a negative pregnancy test. 5. Understood and Signed an informed consent form.

Exclusion Criteria:

• 1. Has central nervous system metastasis or system leukemia. 2.Previous anti-tumor treatment:

  1. Has received IDH1 mutation inhibitor.
  2. Has received systemic anti-tumor therapy or radiotherapy within 14 days before the first dose.
  3. Has received oral targeted drugs, less than 5 drug half-lives from first dose.

  4. The related toxicity of previous anti-tumor therapy has not recovered to CTCAE ≤ grade 2, except for hair loss.

     3.Complicated disease and medical history:

  1. Active hepatitis B or hepatitis C.
  2. Abnormal kidney.
  3. Abnormal cardiovascular and cerebrovascular.
  4. Abnormal gastrointestinal.
  5. Has medical history of immunodeficiency.
  6. Has bleeding (hemoptysis), coagulopathy, or been using warfarin, aspirin, and other antiplatelet agglutination drugs.
  7. Has uncontrollable systemic bacterial, fungal or viral active infections.
  8. Has medical history of idiopathic pulmonary fibrosis,or tissue pneumonia.
  9. Has allergic constitution or previous severe allergy; or known allergy to ingredients of study drug.
  10. Has neurological or mental disorders.
  11. Has a history of drug abuse or drug addict.
  12. Has received major surgery, open biopsy, or obvious traumatic injury within 4 weeks before the first dose.

  13. According to the judgement of the researchers, there are other factors that subjects are not suitable for the study.

      4. Has participated in other clinical trials within 30 days before participating in this trial.

      5. Female patients during pregnancy or lactation. 6. According to the judgement of the researchers, there are other factors that subjects are not suitable for the study.

      7. criteria for solid tumors:

  1. Has any signs of bleeding constitution.
  2. Has any CTCAE ≥ grade 3 bleeding or bleeding event,within 4 weeks before the first dose.
  3. Has unhealed wounds, fractures, active ulcers of the stomach and duodenum, ulcerative colitis and other digestive tract diseases.
  4. Imaging (CT or MRI) shows that the tumor has invaded the circumference of important blood vessels.
  5. Has uncontrollable pleural effusion, pericardial effusion or ascites that still need repeated drainage.

criteria for blood tumor:

a) Has severe life-threatening leukemia complications.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: TQB3454 tablets; TQB3454 tablets administered orally once. Then TQB3454 tablets administered orally, once daily in 28-day cycle after 7 days of first administration.	Drug: TQB3454; TQB3454 tablets is a small molecule oral drug.

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	Cmax is the maximum plasma concentration of TQB3454 or metabolite(s).	Hour 0(pre-dose), 0.5, 1, 2, 3, 5, 8, 10, 24, 48, 72, 120, 168 hours post-dose on single dose;
Tmax	To characterize the pharmacokinetics of TQB3454 by assessment of time to reach maximum plasma concentration.	Hour 0(pre-dose), 0.5, 1, 2, 3, 5, 8, 10, 24, 48, 72, 120, 168 hours post-dose on single dose;
AUC0-t	To characterize the pharmacokinetics of TQB3454 by assessment of area under the plasma concentration time curve from zero to infinity.	Hour 0(pre-dose), 0.5, 1, 2, 3, 5, 8, 10, 24, 48, 72, 120, 168 hours post-dose on single dose;
Objective response rate (ORR)	Percentage of participants achieving complete response (CR) and partial response (PR).	up to 60 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 60 weeks
2-hydroxyglutaric acid	Correlation between 2-hydroxyglutaric acid and efficacy	Hour 0(pre-dose) on single dose; Hour 0(pre-dose) of day1, day8, day15, day28 on multiple dose of first cycle; hour 0(pre-dose) of day15, day28 of second and third cycle; hour 0(pre-dose) of day28 of fourth to eighth cycle.Each cycle is 28 days.

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 24, 2020
• Primary Completion (ANTICIPATED): December 31, 2022
• Study Completion (ANTICIPATED): December 31, 2022

Study Registration Dates

• First Submitted: July 19, 2020
• First Submitted That Met QC Criteria: July 19, 2020
• First Posted (ACTUAL): July 22, 2020

Study Record Updates

• Last Update Posted (ACTUAL): January 10, 2022
• Last Update Submitted That Met QC Criteria: January 6, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: TQB3454-I-02

Drug and device information, study documents

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