TGRX-678 US Phase I for Subjects with Refractory or Advanced Chronic Myelogenous Leukemia

NCT06088888 | Recruiting Phase 1 FDA Drug

• 1 other identifier: TGRX-678-07-101
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this single-arm, open-label, dose escalation + cohort expansion study is to evaluate the safety, tolerability, pharmacokinetic and preliminary efficacy of TGRX-678 in Chronic Myelogenous Leukemia patients who had failure with or are intolerant to TKI treatments.

Conditions

Chronic Myelogenous Leukemia

Outcome Measures

Primary Outcomes (4)

• Recommended dose for expansion (RDE)

  To determine the RDE of TGRX-678 in CML patients to be applied in Cohort Expansion part of the study

  Time Frame: At end of Dose Escalation part of study, an average of 1 year

• Safety profile (DLT)

  to record and analyse subjects with dose-limiting toxicities (DLTs)

  Time Frame: DLT: collect during Cycle 1 (28 days)

• Safety profile (AEs/SAEs)

  to record and analyse subjects with adverse events (AEs) and serious adverse events (SAEs)

  AE and SAE: through completion of the study, an average of 2 years

• Recommended phase II dose (RP2D)

  To determine the RP2D of TGRX-678 in CML patients for Phase II

  At completion of the study, an average of 2 years

Secondary Outcomes (14)

• Hematologic Response

  at screening period, weekly in Cycle 1, bi-weekly in Cycle 2 and monthly starting from Cycle 3 (each cycle is 28 days), an average of 1.5 years

• Cytogenetic Response

  at screening period, end of every 3 Cycles (each cycle is 28 days), an average of 1.5 years

• Molecular Response

  at screening period, end of every 3 Cycles (each cycle is 28 days), an average of 1.5 years

• Plasma Cmax

  Day 1, 7, 21, 28 of Cycle 1, and Day 28 of Cycle 2, 3 and 5 (each cycle is 28 days)

• Plasma Tmax

  Day 1, 7, 21, 28 of Cycle 1, and Day 28 of Cycle 2, 3 and 5 (each cycle is 28 days)

Study Arms (1)

TGRX-678

EXPERIMENTAL

Subjects to be treated with the investigational drug TGRX-678

Drug: TGRX-678

Interventions

TGRX-678 DRUG

Participants are given TGRX-678 tablets orally, once daily, at one of the dose levels as pre-determined for the dose escalation sequence or expansion cohorts.

TGRX-678

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• Shenzhen TargetRx, Inc.: lead
• M.D. Anderson Cancer Center: collaborator

Study Sites (2)

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Fred Hutchinson Cancer Center

Seattle, Washington, 98102, United States

RECRUITING

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Elias Jabbour

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xinyi Zhu

CONTACT

86-13061651609; xinyi.zhu@tjrbiosciences.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 8, 2023
• First Posted: October 18, 2023
• Study Start: July 2, 2024
• Primary Completion (Estimated): March 30, 2027
• Study Completion (Estimated): June 30, 2027
• Last Updated: February 21, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)