TGRX-326 Chinese Phase I for Advanced Non-small Cell Lung Cancer (NSCLC)

NCT05441956 | Active Not Recruiting Phase 1

• 1 other identifier: TGRX-326-1001
• Study Type: interventional
• Target: 198
• Locations: 1 country
• Sites: 1

Brief Summary

This trial is a multi-center, single-arm, open-label, Phase I clinical trial in 3 phases: dose escalation phase, dose expansion phase and indication expansion phase, which will explore the safety, tolerability, PK and preliminary efficacy of TGRX-326 in patients with ALK-positive or ROS1-positive advanced NSCLC.

Conditions

Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (4)

• Maximal tolerated dose (MTD)

  To determine the MTD of TGRX-326 in NSCLC patients

  At end of Cycle 1 (each cycle is 21 days) when the probability of DLT of a dose level is higher than 33%

• Recommended phase II dose (RP2D)

  To determine the RP2D of TGRX-326 in NSCLC patients for Phase II

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

• Safety profile (DLT)

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

  Collect during Cycle 1 (each cycle is 21 days)

• Safety profile (AEs/SAEs)

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

  Through completion of the study, an average of 1.5 years

Secondary Outcomes (17)

• Plasma Cmax

  Day1/3 of single-dose period; Day1/8/15 of Cycle 1; Day1 of Cycle 2-5, Day 1 of every other cycle starting from Cycle 7; Day 1 of every 4 cycles starting from Cycle 17 (each cycle is 21 days)

• Plasma Tmax

  Day1/3 of single-dose period; Day1/8/15 of Cycle 1; Day1 of Cycle 2-5, Day 1 of every other cycle starting from Cycle 7; Day 1 of every 4 cycles starting from Cycle 17 (each cycle is 21 days)

• T1/2

  Day1/3 of single-dose period; Day1/8/15 of Cycle 1; Day1 of Cycle 2-5, Day 1 of every other cycle starting from Cycle 7; Day 1 of every 4 cycles starting from Cycle 17 (each cycle is 21 days)

• Plasma AUCinf

  Day1/3 of single-dose period; Day1/8/15 of Cycle 1; Day1 of Cycle 2-5, Day 1 of every other cycle starting from Cycle 7; Day 1 of every 4 cycles starting from Cycle 17 (each cycle is 21 days)

• Plasma Cmin

  Day1/3 of single-dose period; Day1/8/15 of Cycle 1; Day1 of Cycle 2-5, Day 1 of every other cycle starting from Cycle 7; Day 1 of every 4 cycles starting from Cycle 17 (each cycle is 21 days)

Other Outcomes (1)

• Cmax, CSF

  Day 1/3 of single-dose period; Day 1/8/15 of Cycle 1; Day 1 of Cycle 2-5, Day 1 of every other cycle starting from Cycle 7; Day 1 of every 4 cycles starting from Cycle 17 (each cycle is 21 days)

Study Arms (1)

TGRX-326

EXPERIMENTAL

Subjects to be treated with the investigational drug TGRX-326

Drug: TGRX-326

Interventions

TGRX-326 DRUG

Participants are given TGRX-326 tablets orally at one of the dose levels as pre-determined.

TGRX-326

Eligibility Criteria

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

You may qualify if:

• Willing to follow the treatment protocol and visit schedule, and participate in the study with the ICF signed;
• ≥ 18 years of age on the day of ICF signing, regardless of gender.
• Diagnosis of ALK-positive or ROS1-positive advanced NSCLC by histopathology or cytology in a Grade-A tertiary hospital or central laboratory.
• Provision of the following information: archived tissue samples and/or fresh tumor tissue samples obtained during the screening period for biomarker detection; previous biomarker detection results from a Grade-A tertiary hospital (exempt from the above-mentioned biomarker detection); previous NGS results; the consent of medical monitors for the participation of subjects who fail to provide tumor tissue samples (e.g., samples are exhausted due to previous diagnostic tests but high clinical risk may be brought about by re-puncture, etc.).
• Metastases to central nervous system (CNS) with the following conditions met: a. asymptomatic: no current need for corticosteroid therapy, or only stable dose or a dose reduced to ≤ 10 mg of prednisone (QD) or equivalent required; or b. past diagnosis, treatment completed, complete recovery from acute effects of radiation therapy or surgery prior to the first dose, discontinuation of corticosteroid therapy for these metastases for at least 4 weeks, and neurologically stable;
• Drug discontinuation for ≥ 5 half-lives prior to the first dose for subjects previously treated with a targeted therapy (e.g., ALK or ROS1 inhibitors);
• At least one measurable (longest diameter for non-lymph nodes: ≥ 10 mm; shortest diameter for lymph nodes: ≥ 15 mm) target lesion (a previously irradiated lesion cannot be regarded as a target lesion unless it is significantly progressive) according to criteria in RECIST version 1.1;
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS): 0-1 point in dose escalation and dose expansion phases; 0-2 points in indication expansion phase;
• Recovery from any AEs associated with prior surgery and cancer therapy (to ≤ Grade 1), with the following exceptions: a. alopecia; b. pigmentation; c. long-term toxicity due to radiotherapy that, in the judgment of the investigator, is not recoverable; d. Grade 2 and below neurotoxicity due to platinum; e. hemoglobin within the range of 90-100 g/L (inclusive);
• Adequate bone marrow, liver, kidney, coagulation and pancreatic functions;
• Expected survival ≥ 3 months;
• Willing to take effective contraceptive measures (for men of reproductive potential and women of reproductive age only) from ICF signing to 6 months after administration of the investigational drug. Women of reproductive age include women in perimenopause and within 2 years after menopause. Those women must have a negative pregnancy test ≤ 7 days prior to the first dose of the investigational drug.

You may not qualify if:

• Previous use of any third-generation ALK inhibitors or second-generation ROS1 inhibitors other than TGRX-326.
• Known hypersensitivity to any of the active ingredients or excipients of TGRX-326; an identified history of allergy to protein-based drugs; a history of atopic allergy (asthma, rheumatism, eczematous dermatitis); previous history of other severe allergic reactions that makes himself/herself unsuitable for TGRX-326 treatment in the judgment of the investigator;
• Having another type of cancer except for lung cancer, excluding malignant tumors including cervical cancer in situ and non-melanoma skin cancer that have been curatively treated and have not recurred within 5 years;
• Having previously received antibodies or pharmacotherapy against T cell costimulation or immune checkpoint pathways, including but not limited to anti-programmed cell death protein 1 (anti-PD-1), anti-programmed cell death protein ligand 1 (anti-PD-1), anti-programmed cell death protein ligand 2 (anti-PD-L2), anti-cluster of differentiation 137 (anti-CD137) antibody or anti-cytotoxic T lymphocyte-associated antigen 4 (anti-CTLA-4) antibody;
• Spinal cord compression, unless the subject achieves significant pain control with treatment and full recovery of neurological function within 4 weeks prior to the first dose.
• Abnormal gastrointestinal function, including the inability to take oral drugs, the need for intravenous nutrition, previous surgical operations (including total gastrectomy or gastric band surgery) that affect absorption, active inflammatory gastrointestinal diseases, chronic diarrhea, symptomatic Diverticular disease, treatment of active peptic ulcer disease or malabsorption syndrome within the past 6 months;
• History of active pneumonia or interstitial pneumonia, or radiation or drug-induced lung disorder on CT at screening. Radiation pneumonia patients without clinical symptoms 3 months after radiotherapy are allowed to be enrolled;
• Cardiac insufficiency, including but not limited to left ventricular ejection fraction (LVEF) \< 50%, history of congestive cardiac failure, ventricular arrhythmia requiring treatment, hypokalemia, hereditary long QT syndrome, or history of myocardial infarction or unstable angina pectoris within 6 months before screening; ≥ Class 2 heart failure in New York Heart Association Classification;
• Abnormal and clinically significant QTc on ECG (\> 450 msec \[male\] or QTc \> 470 msec \[female\] at rest); concomitant use of any drug known to prolong QT interval and cause torsades de pointes;
• Uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg) after drug treatment;
• Susceptibility to acute pancreatitis (e.g., uncontrolled hyperglycemia, current gallstones) as judged by the investigator one month prior to the first dose;
• Severe or uncontrolled systemic diseases (such as unstable or uncompensated respiratory, cardiac, hepatic or renal diseases) causing expected intolerance to the investigational drug as judged by the investigator;
• Use within 14 days before first dose or expected concomitant use during the treatment period of drugs that pose risk of QTC interval prolongation and/or ventricular tachycardia;
• Use of any systemic antineoplastic therapies within 28 days prior to the first dose of trial drug (included if TGRX-326 is allowed within 28 days after the systemic antineoplastic therapy, as assessed by the investigator), including systemic chemotherapy, immunotherapy (physiological replacement dose of glucocorticoids \[prednisone or equivalent \< 10 mg/day\] is allowed, excluding antibodies or drugs against T-cell costimulation or immune checkpoint pathways).
• Treatment with radiotherapy or Chinese herbal medicine or Chinese patent medicine for antineoplastic therapies within 14 days prior to the first dose.

Sponsors & Collaborators

• Shenzhen TargetRx, Inc.: lead
• Sun Yat-sen University: collaborator

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

Location

Related Publications (1)

• Zhao S, Zhou H, Yang N, Wang Z, Jin W, Ma Y, Xue J, Li X, Liu Y, Meng R, Zhou J, Cheng Y, Wang Y, Yu Z, Cao Y, Zhao Y, Huang Y, Fang W, Zhang Y, Hong S, Wu B, Shi Y, Cao J, Xu M, Zhang X, Hu L, Peng B, Yang Y, Zhang L, Zhao H. Safety, Efficacy, and Biomarker Analysis of Deulorlatinib (TGRX-326) in Anaplastic Lymphoma Kinase-Positive NSCLC: A Multicenter, Open-Label, Phase 1/1b Trial. J Thorac Oncol. 2025 Jun;20(6):750-762. doi: 10.1016/j.jtho.2024.11.010. Epub 2024 Nov 15.

  PMID: 39551469 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Li Zhang, MD

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

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: June 23, 2022
• First Posted: July 1, 2022
• Study Start: April 23, 2021
• Primary Completion: August 31, 2025
• Study Completion: October 31, 2025
• Last Updated: May 18, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)