A Clinical Trial to Evaluate the Safety and Tolerability of TQB3911 Tablets in Patients With BCR::ABL Fusion Gene Positive Leukemia

Phase I Clinical Trial to Evaluate the Safety and Tolerability of TQB3911 Tablets in Patients With BCR::ABL Fusion Gene Positive Leukemia

Phase I clinical trial to explore the safety, tolerability, and initial efficacy of TQB3911 tablets in BCR::ABL fusion gene positive leukemia.

Study Overview

• Status: Not yet recruiting
• Conditions: Chronic Myelogenous Leukemia
• Intervention / Treatment: Drug: TQB3911 tablets

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Qian Jiang, Doctor; Phone Number: 010-88326850; Email: jiangqian@medmail.com.cn

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100044
      • Peking University People's Hospital
      • Contact: Li Zhou, Doctor; Phone Number: 13816510379; Email: 13816510379Lizhou999_999@126.com
  • Guangxi
    • Nanning, Guangxi, China, 530021
      • The First Affiliated Hospital of Guangxi Medical University
  • Henan
    • Zhengzhou, Henan, China
      • Henan Cancer Hospital
      • Contact: Jian Huang, Doctor; Phone Number: 13588010568
  • Shanghai
    • Shanghai, Shanghai, China, 200025
      • Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
      • Contact: YanLi Zhang, Doctor; Phone Number: 13203729690; Email: 13203729690@163.com
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310006
      • The First Affiliated Hospital of Zhejiang University School of Medicine
      • Contact: Zhenfang Liu, Doctor; Phone Number: 13481082237; Email: liuliuzhenfang@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• The subjects voluntarily joined the study, signed the informed consent, and had good compliance;
• Age: ≥18 years old (when signing the informed consent); Eastern Cooperative Oncology Group Performance Status (ECOG PS) score: 0-2; Expected survival of more than 3 months;
• During the screening period, the patients were identified as Chronic myelogenous leukemia-Chronic phase (CML-CP) or accelerated phase (AP) patients by bone marrow cell morphological examination, molecular biological examination or cytogenetic examination;
• Chronic myelogenous leukemia (CML) patients who are intolerant to Tyrosine kinase inhibitors (TKI) drugs or whose therapeutic effect is not satisfactory (that is, the therapeutic response evaluation result is failure)
• The main organs function well
• Female subjects of reproductive age should agree to use contraceptives (such as Iuds, contraceptives, or condoms) during the study period and for 6 months after the end of the study; Have a negative serum pregnancy test within 7 days prior to study enrollment and must be a non-lactating subject; Male subjects should agree to use avoidance during the study period and for 6 months after the end of the study period.

Exclusion Criteria:

• Had or was currently suffering from other malignant tumors within 5 years before the first medication
• Combined with active central nervous system leukemia
• Major surgical treatment and significant traumatic injury were received within 28 days before the start of study treatment
• Previous history of myocardial infarction, pulmonary hypertension, or angina pectoris within 3 months before the first medication, or clinically significant arrhythmias such as ventricular tachycardia, complete left bundle branch block, and high atrioventricular block
• Acute pancreatitis and a history of chronic pancreatitis within 12 months before the first medication
• History of interstitial lung disease, radiation pneumonia requiring steroid treatment, or drug-related pneumonia
• Patients with CML-CP who have achieved complete cytogenetic response (CCyR)
• Received live attenuated vaccine within 4 weeks before the first dose, or planned to receive live attenuated vaccine during study participation
• Use of drugs that may have caused QT prolongation or tip torsical tachycardia in the 7 days prior to initial administration, or continuation of these medications during the study period

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: TQB3911 tablets; Once a day for 28 days as a treatment cycle	Drug: TQB3911 tablets; TQB3911 is a small molecule BCR::ABL1 allosteric inhibitor. By occupying the myristyl binding site, TQB3911 recovers the inhibition of BCR::ABL1 fusion protein kinase activity, and ultimately inhibits the proliferation of tumor cells.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase II recommended doses (RP2D)	The dosage of drug therapy recommended for use in the second phase of clinical trials (i.e., phase II clinical trials).	Baseline up to 24 months
Dose-limiting toxicity (DLT)	Adverse events that meet the protocol definition of dose-limiting toxic event timing were evaluated according to the Common Terminology Criteria for Adverse Events 5.0.	Up to 1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and severity of adverse event (AE) and serious adverse event (SAE), and abnormal laboratory test indicators	Incidence and severity of AE and SAE, and abnormal laboratory test indicators	From the signing of informed consent for administration to 28 days after the last administration/start of the new antitumor therapy (whichever occurs first).
Peak time	Time to peak blood concentration after a single dose	Single dose on days 1 to 3, day 8 of cycle 1, day 15 of cycle 1, day 22 of cycle 1, and day 2 to day 1, each cycle is 28 days.
C-QT Research	Effect of TQB3911 on QTcF interval in subjects	Single dose: 1 hour, 0.5 hour, 10 minutes before dose and 0.5 hour, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 8 hours, 12 hours, 24 hours after dose.
Platelet count	Hematologic remission of subjects during treatment	For the first six weeks, the assessment was weekly. Starting at week 6, assessments were performed at week 8 and every 4 weeks (±7 days) thereafter
The proportion of Philadelphia chromosomes in the metaphase of bone marrow cells	Cytogenetic remission of subjects during treatment	They were evaluated every 12 weeks (±7 days) for 96 weeks and every 24 weeks (±7 days) after 96 weeks
Molecular reaction	Molecular remission of subjects during treatment	They were evaluated every 12 weeks (±7 days) for 96 weeks and every 24 weeks (±7 days) after 96 weeks
Progression free survival	The period of time between the subject's treatment and the observation of disease progression or death from any cause	They were evaluated every 12 weeks (±7 days) for 96 weeks and every 24 weeks (±7 days) after 96 weeks
Overall survival	The time from the subject's initiation of treatment or diagnosis until the patient's death from any cause	They were evaluated every 12 weeks (±7 days) for 96 weeks and every 24 weeks (±7 days) after 96 weeks
Peak concentration Cmax	After a single dose, the highest point of the drug-time curve is called the peak concentration	Single dose on days 1 to 3, day 8 of cycle 1, day 15 of cycle 1, day 22 of cycle 1, and day 2 to day 1, each cycle is 28 days.
Plasma elimination half-life t1/2	The amount of time it takes for the concentration of the drug in the blood, or the amount of drug in the body, to drop to about half of its original level.	Single dose on days 1 to 3, day 8 of cycle 1, day 15 of cycle 1, day 22 of cycle 1, and day 2 to day 1, each cycle is 28 days.

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2024
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: October 27, 2024
• First Submitted That Met QC Criteria: October 31, 2024
• First Posted (Estimated): November 4, 2024

Study Record Updates

• Last Update Posted (Estimated): November 4, 2024
• Last Update Submitted That Met QC Criteria: October 31, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Chronic Disease; Disease Attributes; Neoplasms by Histologic Type; Hematologic Diseases; Bone Marrow Diseases; Myeloproliferative Disorders; Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Other Study ID Numbers: TQB3911-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