TGRX-814 Chinese Phase I/II in Patients With Hematological Malignancies

NCT06206174 | Recruiting Phase 1

• 1 other identifier: TGRX-814-1001
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this single- arm, open-label, dose escalation and dose expansion phase I/II study is to evaluate the safety, tolerability, pharmacokinetic and preliminary efficacy of TGRX-814 in patients with hematological malignancies including non-Hodgkin lymphoma, acute myeloid leukemia, aute lymphoblastic leukemia and myelodysplastic syndromes.

Conditions

Hematologic Malignancy; Non Hodgkin Lymphoma; Acute Myeloid Leukemia; Acute Lymphoblastic Leukemia, Adult; Myelodysplastic Syndromes

Outcome Measures

Primary Outcomes (2)

• Maximal tolerated dose (MTD)

  To determine the MTD of TGRX-814 in non-Hodgkin lymphoma (NHL) patients

  At end of dose escalation when the probability of DLT of a dose level is greater than 0.359

• Recommended phase II dose (RP2D)

  To determine the RP2D of TGRX-814 in NHL patients for Phase II

  At completion of the dose escalation study, an average of 1 year

Secondary Outcomes (23)

• Dose-limiting toxicities (DLTs)

  DLT is collected during Cycle 1 (each cycle is 28 days)

• Adverse Events (AEs)/Serious Adverse Events (SAEs)

  AE and SAE are collected throughout and until completion of the study, an average of 1 year.

• Complete Response (CR) rate

  at screening period, at the end of week 8, 16, 24, 36, 48, subsequent every 24 weeks and the last visit of treatment period, at the end-of-treatment follow-up visit and safety follow-up visit

• Complete response with incomplete count recovery (CRi) rate

  at screening period, at the end of week 8, 16, 24, 36, 48, subsequent every 24 weeks and the last visit of treatment period, at the end-of-treatment follow-up visit and safety follow-up visit

• Partial response (PR) rate

  at screening period, at the end of week 8, 16, 24, 36, 48, subsequent every 24 weeks and the last visit of treatment period, at the end-of-treatment follow-up visit and safety follow-up visit

Study Arms (1)

TGRX-814

EXPERIMENTAL

TGRX-814 monotherapy for Dose escalation study; oral, once daily administration.

Drug: TGRX-814

Interventions

TGRX-814 DRUG

Participants are given TGRX-814 tablets for oral, once daily administration at one of the dose levels as pre-determined for the dose escalation sequence.

Also known as: TGRX-814 monotherapy

TGRX-814

Eligibility Criteria

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

You may qualify if:

• male or female ≥ 18 years of age
• fully understand the requirements of the study and voluntarily sign a written informed consent form
• diagnosis of NHL, ALL, AML or MDS
• Eastern Cooperative Oncology Group (ECOG) physical status score ≤ 2
• adequate bone marrow function
• patients at high risk for Tumor Lysis Syndrome (TLS) determined by investigator and sponsor for agreement to enroll
• adequate disease indicator
• adequate coagulation, hepatic and renal function
• female subjects of childbearing potential and male subjects whose partners are women of childbearing potential must agree to use a medically approved highly effective contraceptive from the time of signing the Informed Consent Form until at least 3 months after the last dose of study drug; women of childbearing potential must have a negative blood or urine pregnancy test within 7 days prior to the first dose of study drug
• Expected survival time ≥ 12 weeks

You may not qualify if:

• received BCL-2 inhibitor therapy prior to the first dose of study drug, unless discontinued due to intolerance
• subjects with NHL have been diagnosed with Burkitt's lymphoma, lymphoblastoid lymphoma/leukemia, or post-transplant lymphoproliferative disease (PTLD)
• AML subjects with a diagnosis of acute promyelocytic leukemia or Ph chromosome positive or persistent extramedullary leukemia
• tumor infiltration of the central nervous system
• received allogeneic hematopoietic stem cell transplantation; or received autologous hematopoietic stem cell transplantation within 3 months
• received vaccination within 4 weeks prior to first dose or scheduled to be vaccinated during the study
• HBsAg-positive or HBcAb-positive; HCV antibody-positive; HIV antibody-positive
• monoclonal antibody antitumor therapy within 4 weeks prior to the first dose; participation in a clinical trial of another interventional drug within 4 weeks prior to the first dose; participation in CAR-T therapy within 12 weeks prior to the first dose; 9. 14 weeks prior to the first dose
• received anticancer therapy/investigational therapy within 14 days prior to the first dose, or has not recovered from clinically significant toxicity below grade 2 on prior therapy
• received steroidal anticancer therapy, CYP3A inhibitors, or CYP3A inducers within 7 days prior to the first dose of study drug
• consumption of grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges), or popcorn within 3 days prior to the first dose of the drug
• poorly controlled hypertension; left ventricular ejection fraction ≤ 50% as assessed by cardiac ultrasound; prolonged QT interval; Grade III atrioventricular block or other arrhythmia requiring medical intervention; New York Heart Association (NYHA) Class III or IV congestive heart failure; had myocardial infarction or experienced bypass surgery within 6 months prior to dosing; had arterial or venous thrombotic events within 6 months prior to the first dose of study drug; have other cardiovascular diseases that investigator deemed unfit for enrollment
• having a history of renal, neurological, psychiatric, pulmonary, endocrine, metabolic, immunologic, cardiovascular, or hepatic disease that, in the opinion of the Investigator, would adversely affect the subject's participation in this study
• having a history of active malignancy other than NHL, AML, or MDS within 3 years prior to participation in this clinical study
• having a condition of malabsorption syndrome or multiple factors that interfere with the oral administration and absorption of medication

Sponsors & Collaborators

• Shenzhen TargetRx, Inc.: lead
• Institute of Hematology & Blood Diseases Hospital, China: collaborator

Study Sites (1)

Institute of Hematology & Blood Diseases Hospital

Tianjin, Tianjin Municipality, 300020, China

RECRUITING

MeSH Terms

Conditions

Hematologic Neoplasms; Lymphoma, Non-Hodgkin; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Myelodysplastic Syndromes

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoma; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid; Leukemia; Leukemia, Lymphoid; Bone Marrow Diseases

Study Officials

• Jianxiang Wang, MD

  Institute of Hematology & Blood Diseases Hospital, China

  PRINCIPAL INVESTIGATOR

• Bo Jiang, MD

  Institute of Hematology & Blood Diseases Hospital, China

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kai Yan

CONTACT

+8613754709367; kai.yan@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: January 4, 2024
• First Posted: January 16, 2024
• Study Start: March 6, 2024
• Primary Completion: February 28, 2025
• Study Completion (Estimated): February 28, 2029
• Last Updated: April 10, 2024

Record last verified: 2024-04

Locations

CN (1)