TGRX-678 Chinese Phase II in Chronic Myelogenous Leukemia (CML) Patients

A Single-arm, Open-label, Multi-center Phase II Study Evaluating Efficacy and Safety of TGRX-678 in CML-AP Patients Relapsed or Refractory from 3rd-generation TKI Treatment

A Phase II study evaluating the safety and efficacy of TGRX-678 in Chronic Myelogenous Leukemia (CML) patients in Accelerated phase (AP) and are relapsed or refractory from third-generation Tyrosine Kinase Inhibitor (TKI) treatment

Study Overview

• Status: Recruiting
• Conditions: Chronic Myeloid Leukemia; Accelerated Phase CML
• Intervention / Treatment: Drug: TGRX-678

Detailed Description

This Phase II study is of single-arm, open-label and multi-center designs to study safety and efficacy profiles of TGRX-678 in CML-AP patients. Patients need to have medical history of failing treatment(s) from third-generation TKI drugs. Patients with or without T315I mutation is enrolled.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yingkun Lu; Phone Number: 18602219981; Email: yingkun.lv@tjrbiosciences.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100044
      • Recruiting
      • Peking University People's Hospital
      • Contact: Qian Jiang, MD; Phone Number: 010-88326666; Email: Jiangqian@medmail.com
      • Contact: Qian Jiang, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Willing to consent
• 18 years of age or above at time of screening; both sexes eligible
• Relapsed or refactory from 3rd-generation Tyrosine kinase inhibitor (TKI) treatment
• For patients without T315I mutation, the patients must received 1st, 2nd and 3rd generation TKI
• For patients with T315I mutation, the patients much received Olverembatinib or Ponatinib treatment
• Diagnosis of CML-AP by bone marrow morphological test, molecular biology test or cytogenetic tests
• ECOG score </=2
• Minimum life expectancy of at least 3 months
• Adequate hematological indicators
• Adequate kidney function
• Adequate liver function
• Adequate coagulation function
• Adequate pancreatic function
• Adequate QTc interval as confirmed by electrocardiogram (ECG) test
• Negative pregnancy result at screening for female patients of child-bearing potential
• Willing to take contraceptive measure during the study (For male and female patients of child-bearing potential)

Exclusion Criteria:

• Reception of TKI treatment or presence of unrecovered TKI treatment related non-hematological adverse events within 7 days of first dose
• Reception of other anti-tumor treatments
• In need for immune suppressive treatment
• Usage of drugs associated with Torsades de Pointes within 1 months before screening
• Presence of other medical conditions that require using treatment that may have drug-drug interaction with the investigational drug
• History of hemapoietic stem cell transplant
• Presence of active central nervous system conditions
• CML-AP patients who already reached major hematological response
• CML-AP patients who used to progress to Blast Phase (BP)
• Presence or having uncontrolled condition for cardiovascular diseases
• History of any heart or cardiovascular conditions (except for patients with hypertension which is controlled by anti-hypertensive drugs, and blood pressure is controlled at no higher than 160/100 mmHg for 1 months before screening)
• Usage of any Traditional Chinese Medicine indicated for anti-tumor purpose 2 weeks before first dose
• Severe hemorrhagic disease unrelated to CML
• History of severe cardiovascular condition during past TKI treatment for CML
• History of pancreatic inflammation or alcohol abuse within 3 years before first dose
• Uncontrolled Hypertriglyceridemia
• Presence of malabsorption or other conditions that may affect drug absorption
• Diagnosis of other primary malignant tumor within 5 years
• Reception of major surgery 14 days before first dose
• Presence of continuous or active infection (including HIV, hepatitis B, hepatitis C)
• Presence of other conditions that the investigators or medical monitor deem unfit 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: Experimental: TGRX-678; All patients with CML-AP to be treated with TGRX-678. Patients with T315I mutation or without T315I mutation will be assigned into separate cohorts for evaluation	Drug: TGRX-678; All patients will be given TGRX-678 240 mg once daily. TGRX-678 is to be taken orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major Hematologic Response (MaHR)	Number of patients who reached, and rate of occurence of major hematologic response, including those who reached complete hematologic response (CHR) or no evidence of leukemia (NEL). CHR and NEL are defined per China national treatment guideline for CML (ver. 2022). Indicators for hematologic responses will be obtained via peripheral blood tests.	At screening, on Day 1 of every treatment cycle (each cycle is 28 days) and at end of treatment; average of study duration is 3.5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cytogenetic Response	Number of patients who reached, and rate of occurence of cytogenetic response, including those with major cytogenetic response (MCyR) or complete cytogenetic response (CCyR). Cytogenetic responses are defined per China national treatment guideline for CML (ver. 2022). Indicators for cytogenetic responses will be obtained via bone marrow biopsy.	At screening, on Day 1 of cycle 2, cycle 4 and every 3 cycles afterwards of the treatment cycle (each cycle is 28 days) and at the end of treatment; average of study duration is 3.5 years
Major Molecular Response (MMR)	Number of patients who reached, and rate of occurence of MMR. Cytogenetic response is defined per China national treatment guideline for CML (ver. 2022). Indicators for molecular responses will be obtained via genetic testing on transcript levels of BCR-ABL gene.	At screening, on Day 1 of cycle 2, cycle 4 and every 3 cycles afterwards of the treatment cycle (each cycle is 28 days) and at the end of treatment; average of study duration is 3.5 years
Time to Response (TTR)	TTR defined by the time from the start of treatment to the first efficacy response; TTR as evaluated by investigator	At screening, on Day 1 of cycle 2, cycle 4 and every 3 cycles afterwards of the treatment cycle (each cycle is 28 days) and at the end of treatment; average of study duration is 3.5 years
Duration of Response (DOR)	DOR defined as the duration from first occurence of treatment response to progressive disease/relapse; DOR as evaluated by investigator	At screening, on Day 1 of cycle 2, cycle 4 and every 3 cycles afterwards of the treatment cycle (each cycle is 28 days) and at the end of treatment; average of study duration is 3.5 years
Progression Free Survival (PFS)	PFS defined as the time from enrollment to progressive disease or death of any cause; PFS as evaluated by investigator.	At screening, on Day 1 of cycle 2, cycle 4 and every 3 cycles afterwards of the treatment cycle (each cycle is 28 days) and at the end of treatment; average of study duration is 3.5 years
Overall Survival (OS)	OS defined as the time from enrollment to death of any cause; OS as evaluated by investigator	At screening, on Day 1 of cycle 2, cycle 4 and every 3 cycles afterwards of the treatment cycle (each cycle is 28 days) and at the end of treatment; average of study duration is 3.5 years
Treatment Emergent Adverse Event (TEAE)	To record and analyse the occurence and frequency of adverse events during the study	Through completion of the study, an average of 3.5 years

Collaborators and Investigators

• Sponsor: Shenzhen TargetRx, Inc.
• Collaborators: Peking University People's Hospital; Henan Cancer Hospital; Shengjing Hospital; First Affiliated Hospital of Zhejiang University; The First Affiliated Hospital of Soochow University; Shenzhen Second People's Hospital; Tongji Medical College,Huazhong University of Science &Techonlogy; Ruijin Hospital, The Shanghai Jiao Tong University Medical School; Nanfang Hospital, Southern Medical University; Blood Diseases Hospital & Institute of Hematology, Chinese Academy of Medical Sciences & Peking Union Medical College
• Investigators: Principal Investigator: Qian Jiang, MD, Peking University People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 15, 2024
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): April 30, 2028

Study Registration Dates

• First Submitted: May 28, 2024
• First Submitted That Met QC Criteria: June 5, 2024
• First Posted (Actual): June 12, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 19, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Chronic Disease; Disease Attributes; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Bone Marrow Diseases; Myeloproliferative Disorders; Leukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Accelerated Phase
• Other Study ID Numbers: TGRX-678-2001

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