Evaluating TGRX-678 for patients with advanced Chronic Myelogenous Leukemia

A Single-arm, Open-label, Dose Escalation + Cohort Expansion Phase 1 Trial on Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of TGRX-678 in Subjects with Refractory or Advanced Chronic Myelogenous Leukemia

This study is testing a new drug called TGRX-678 to see if it can help people with advanced Chronic Myelogenous Leukemia who haven't had success with other treatments.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 90 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Shenzhen TargetRx Co., Ltd. (Industry-sponsored)
• Locations: 2 sites (Houston, Texas and 1 other locations)
• Trial ID: NCT06088888 on ClinicalTrials.gov

What this trial studies

This is a single-arm, open-label Phase I trial designed to assess the safety, tolerability, pharmacokinetics, and preliminary efficacy of TGRX-678 in patients with refractory or advanced Chronic Myelogenous Leukemia (CML) who have failed or are intolerant to TKI treatments. The study will involve dose escalation and cohort expansion to determine the recommended dose for further trials. Participants will be monitored for adverse events and changes in disease markers to evaluate the drug's effectiveness. This is the first trial of TGRX-678 conducted in the US.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with a diagnosis of Chronic Myelogenous Leukemia who are intolerant or resistant to TKI therapies.

Not a fit: Patients who have recently been exposed to other antineoplastic therapies or investigational agents may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced CML who have limited treatment choices.

How similar studies have performed: While this is the first trial of TGRX-678, similar studies targeting refractory CML have shown promise in the past.

Eligibility criteria

Inclusion Criteria:

* Willing to participate in the study with informed consent;
* At least 18 years of age at the time of screening;
* Any sex;
* Diagnosis of CML-CPduring the screening period;
* Intolerant or resistant to TKI treatments;
* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2;
* Adequate Absolute neutrophil count (ANC), hemoglobin and platelets levels;
* Adequate renal and liver function;
* Normal corrected QT (QTcF) interval as indicated by electrocardiogram (ECG) screening results;
* Negative blood pregnancy test results for female patients of childbearing potential.
* Willing to take highly effective contraceptive measures throughout the trial and for 6 months after last dose of investigational drug for female subjects of child-bearing potential or male subject with female partner of child-bearing potential.

Exclusion Criteria:

* Exposure to other antineoplastic therapies prior to study enrollment;
* Exposure to other investigational agent(s) within 14 days of initiating TGRX-678 therapy;
* Ongoing toxicity from prior therapy greater than grade 1 by CTCAE v. 3 (except alopecia);
* Hematopoietic cell transplantation \< 60 days prior to the first dose;
* Evidence of graft versus host disease (GVHD), whether or not requiring immunosuppressive therapy;
* Concomitant immunosuppressive therapy (other than short-term corticosteroid treatment);
* Exposure to drugs related to torsade de pointes;
* Cytological or pathological diagnosis of active central nervous system disorder;
* Significant or uncontrolled cardiovascular diseases as defined in the full clinical protocol;
* Having long QT syndrome, or with family history of idiopathic sudden death or congenital long QT syndrome;
* Uncontrolled hypertension;
* Receipt of Traditional Chinese medication or herbal preparations indicated for anti-cancer purposes within 2 weeks prior to the first dose;
* Severe hemorrhagic disorders unrelated to CML;
* History of pancreatitis;
* History of excessive alcohol use;
* History of elevation in amylase or lipase within 1 year;
* Have Grade 2 or worse interstitial lung disease or interstitial pneumonitis within 4 weeks prior to Screening;
* Uncontrolled hypertriglyceridemia;
* Malabsorption syndrome or other illness that could affect oral absorption.
* Diagnosis of another primary malignancy in the past 3 years;
* Reception of major surgery within 14 days prior to the first dose;
* Active infections that require systemic treatment or other severe infections within 14 days prior to enrollment;
* Known human immunodeficiency virus (HIV) positive; acute or chronic liver disease (including chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections);
* Have received or will receive a COVID-19 vaccine within 14 days of study enrollment;
* Have a positive reverse transcriptase polymerase chain reaction (RT-PCR) test result for SARS-CoV-2 within 2 weeks prior to Screening;
* Pregnant or breastfeeding female;
* Female patient of child-bearing potential or male patient who have female partners of child-bearing potential that is unable or unwilling to take highly effective contraceptive measures during the trial and for 6 months after last dose of investigational drug;
* Significant organ dysfunction that could compromise the patient's safety or the evaluation of the drug's safety in the opinion of the investigator or the medical monitor;
* Any condition makes participation in this trial inappropriate in the opinion of the investigator or medical monitor;

Where this trial is running

Houston, Texas and 1 other locations

• The University of Texas MD Anderson Cancer Center — Houston, Texas, United States (Recruiting)
• Fred Hutchinson Cancer Center — Seattle, Washington, United States (Recruiting)

Study contacts

• Principal investigator: Elias Jabbour — M.D. Anderson Cancer Center
• Study coordinator: Xinyi Zhu

Conditions Chronic Myelogenous Leukemia