Non-small Cell Lung Cancer
Conditions
Interventions
5mg:TGRX-326 5mg qd
10mg:TGRX-326 10mg qd
20mg:TGRX-326 20mg qd
40mg:TGRX-326 40mg qd
60mg:TGRX-326 60mg qd
80mg:TGRX-326 80mg qd
100mg:TGRX-326 100mg qd
125mg:TGRX-326 125mg qd
Sponsors
Sun Yat-sen University Cancer Center
Eligibility
Sex/Gender
All
Age
18 Years to 100 Years
Inclusion criteria
Inclusion criteria: 1. Willing to follow the treatment protocol and visit schedule, and participate in the study with the ICF signed; 2. = 18 years of age on the day of ICF signing, regardless of gender. 3. Diagnosis of ALK-positive or ROS1-positive advanced NSCLC by histopathology or cytology in a Grade-A tertiary hospital or central laboratory. 4. 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.). 5. Metastases to central nervous system (CNS) is allowed 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; 6. 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); 7. 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; 8. 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; 9. 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); 10. Adequate bone marrow, liver, kidney, coagulation and pancreatic functions; 11. pected survival = 3 months; 12. 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.
Exclusion criteria
Exclusion criteria: 1. Previous use of any third-generation ALK inhibitors or second-generation ROS1 inhibitors other than TGRX-326. 2. 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; 3. 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; 4. Major surgery within 4 weeks prior to the first dose. Minor surgery such as infusion port placement is not listed in the exclusion criteria, but sufficient time is required to achieve adequate wound healing; 5. 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. 6. 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; 7. 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; 8. Cardiac insufficiency, including but not limited to left ventricular ejection fraction (LVEF) 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; 10. Uncontrolled hypertension (systolic blood pressure = 160 mmHg or diastolic blood pressure = 100 mmHg) after drug treatment; 11. Susceptibility to acute pancreatitis (e.g., uncontrolled hyperglycemia, current gallstones) as judged by the investigator one month prior to the first dose; 12. 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; 13. 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; 14. 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 r
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety;Tolerability; | — |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetics;Efficacy; | — |
Countries
China
Contacts
Public ContactLi Zhang
Sun Yat-sen University Cancer Center
Outcome results
None listed