TGRX-1942 Chinese Phase I for Advanced Solid Tumor And/or Relapsed/Refractory Hematologic Malignancies

Official title

A Dose Escalation and Expansion Phase I Study Evaluating the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of TGRX-1942 in Patients with Advanced Solid Tumor And/or Relapsed/Refractory Hematologic Malignancies

Overview

A phase I study to evaluate the safety, tolerability, pharmacokinetics and preliminary efficacy of TGRX-1942 in patients with advanced solid tumor and/or relapsed or refractory hematological malignancies

Detailed description

This study is designed as a three-part study, with dose escalation, dose expansion and indication expansion phases. Patients with advanced solid tumors will be initially enrolled to the study. Other indications including solid tumors with specific gene mutations, or other hematological malignancies with be considered for expansion phases, with appropriate doses as evaluated at the end of dose escalation phase.

Interventions

• Drug TGRX-1942
  At dose escalation phase, TGRX-1942 will be given orally to patient once a day under a 7-dose sequence of 4mg, 10mg, 20mg, 30mg, 40mg, 50mg, and 60mg. The dose level a particular patient will be assigned depends on the progression of the study and PI evaluation on the safety of previous dose group(s).

Primary outcome measures

• Adverse events/serious adverse events [Time frame: From screening through completion of the study, an average of 3.5 years.]
• Maximum Tolerated Dose (MTD) [Time frame: From Day 1 of Cycle 1 to Day 28 of Cycle 1 of dose escalation phase (each cycle is 28 days)]

Secondary outcome measures (11)

• Preliminary efficacy [Time frame: From screening, every 3 cycles during treatment period (each cycle is 28 days) and at end of study, an average of 3.5 years.]
• Time to Maximum Concentration (Tmax) [Time frame: On day 1-6 of the single dosing phase; patient will only be dosed once on Day 1 of this phase]
• Maximum Concentration (Cmax) [Time frame: On day 1-6 of the single dosing phase; patient will only be dosed once on Day 1 of this phase]
• Area Under Curve (AUC0-t) [Time frame: On day 1-6 of the single dosing phase; patient will only be dosed once on Day 1 of this phase]
• Half life (T1/2) [Time frame: On day 1-6 of the single dosing phase; patient will only be dosed once on Day 1 of this phase]
• Apparent Clearance (CL/F) [Time frame: On day 1-6 of the single dosing phase; patient will only be dosed once on Day 1 of this phase]
• Apparent Volume of Distribution (Vz/F) [Time frame: On day 1-6 of the single dosing phase; patient will only be dosed once on Day 1 of this phase]
• Steady State Time to Maximal Concentration (Tmax,ss) [Time frame: On day 1 of Cycle 1 of dose escalation phase (each cycle is 28 days)]
• Steady State Maximal Concentration (Cmax,ss) [Time frame: On Day 1, 8, 15 and 22 of Cycle 1 and Day 1 of every 3 cycles (each cycle is 28 days). Average duration of the treatment period is 3 years.]
• Steady State Trough Concentration (Ctrough,ss) [Time frame: On Day 1, 8, 15 and 22 of Cycle 1 and Day 1 of every 3 cycles (each cycle is 28 days). Average duration of the treatment period is 3 years.]
• Steady State Area Under Curve (AUC0-t,ss) [Time frame: On Day 1, 8, 15 and 22 of Cycle 1 and Day 1 of every 3 cycles (each cycle is 28 days). Average duration of the treatment period is 3 years.]

Eligibility criteria

Inclusion criteria

• For dose escalation phase, patient is diagnosed with advanced/metastatic solid tumor who had failed standard therapies and does not have available effective treatment, or who relapsed from prior treatments
• ECOG score of equals to or lower than 1
• Life expectancy of at least 3 months
• Adequate systemic and organ functions, including hematologic, hepatic and kidney functions
• Willing to provide available tumor biopsy sample or reports, or willing to undergo tumor biopsy examination, and willing to partake whole blood sampling for evaluations
• For female of child-bearing potential, willing to undergo plasma pregnancy test 28 days before first dose and have negative results
• Male and Female of child-bearing potential must agree to take effective contraceptive measures during the entire treatment period and for 2 months after the end of treatment
• Understand and willing to sign informed concent; willing and able to complete the visiting schedule and other tasks as required for the study

Exclusion criteria

• Allergic to any of the ingredient of the investigational drug
• History of other primary malignancies
• Have adverse/toxic effects from previous treatment that has not recovered to CTCAE 5.0 <= Grade 1
• Received other anti-tumor treatments (i.e., chemotherapy, biologics, immunotherapy, targeted therapy, etc.) 28 days before first dose, or radiation therapy 14 days before first dose
• Used drugs known to significantly affect P450 metabolism 2 weeks before first dose
• Participated in other clinical trials and used other investigational agents 28 days before first dose
• Received major surgeries or had traumatic injuries 28 days before first dose
• Need to use concomitant drugs that could cause QTc elongation or induce Torsades de Pointes
• History or presence of other medical conditions, such as HIV/HBV/HCV positive; received anticoagulation treatment; coagulation dysfunction; major or clinically significant cardiovascular disease; pneumonia; clinically significant gastrointestinal abnormalities that could affect drug absorption; uncontrollable hypertension; ulcer in abdomen, intestine, stomach, trachea or esophagus; uncontrolled seizure or have other central nervous system diseases, poorly managed diabetes; long QT syndrome; uncontrolled active infections; uncontrolled pericardial or abdominal effusion; adrenaline malfunction; thyroid dysfunction; severe unhealed wound, ulcer or bone fractures; Toxic epidermal necrolysis; Stevens-Johnson syndrome
• Have symptomatic or uncontrolled primary or metastatic central nervous system tumor or Leptomeninges tumor, or untreated diseases that cause compressions to spinal cords
• For female patients: in pregnancy or breast-feeding periods
• Presence of any condition or history that could affect study results or participation to the study in the judgement of the investigator
• Used immunosuppressant drugs within14 days before first dose
• Received vaccine injection within 30 days of Cycle 1 Day 1

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Sir Run Run Shaw Hospital, Zhejiang University School of Medicine — Hangzhou

Identifiers

NCT: NCT06484816 · TGRX-1942-1001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗