This is a multi-center, randomized, open-label, Phase III clinical trial which compares the safety and efficacy of TGRX-326 with crizotinib in patients with ALK-positive advanced or metastatic NSCLC

This Phase III study aims to evaluate the safety profile and efficacy profile in patients with ALK-positive advanced or metastatic NSCLC and to compare the efficacy and safety of TGRX-326 with that of crizotinib. The primary purpose of this study is to evaluate and compare the efficacy profile of TGRX-326 with crizotinib, with progression-free survival (PFS) as evaluated by independent review committee (IRC) as end point. Secondary objectives include comparing efficacy profile of other endpoints and safety profiles of the investigational drug with crizotinib. Exploratory objective includes the evaluation of population pharmacokinetic (PK) profile of TGRX-326 and efficacy of TGRX-326 in ALK-positive advanced NSCLC patients determined as progressive disease after crizotinib treatment.

Inclusion Criteria:

• 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.
• Diagnosed as incurable stage IIIB - IV ALK-positive NSCLC;
• Providing prior ALK positive test results at screening;
• Naïve to ALK-inhibitor; patients could be intolerant or have progressive disease from previous first-line chemotherapy;
• Patients could have metastases to central nervous system at screening if the condition is asymptomatic, stable or completely recovered;
• At least one measurable lesion;
• An ECOG PS score within 0-2;
• 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 last administration of the investigational drug. Women of reproductive age include women before menopause and within 1 year after menopause; those women must have a negative pregnancy test ≤ 7 days prior to the first dose of the investigational drug.

Exclusion Criteria:

• Known hypersensitivity to any of the active ingredients or excipients of TGRX-326 or crizotinib pills; or a history of severe allergic reactions;
• Having another type of cancer except for lung cancer;
• Radiotherapy within 14 days prior to the first dose;
• Received other systemic anti-tumor treatment within 4 weeks prior to the first dose, or is within 5 half-lives of the said treatment; received traditional Chinese medicine indicated for anti-tumor purposes within 14 days prior to the first dose;
• Major surgery within 4 weeks prior to the first dose;
• Spinal cord compression caused by tumor, unless the subject achieves significant pain control and full recovery of neurological function within 4 weeks prior to the first dose.
• Abnormal gastrointestinal function that affect absorption within the past 6 months;
• History of active pneumonia or clinically significant interstitial pneumonia, or radiation or drug-induced lung disorder with treatment needs;
• Cardiac insufficiency;
• Abnormal and clinically significant QTc on ECG or need of concomitant use of any drug known to prolong QT interval and cause torsades de pointes;
• Uncontrolled hypertension after drug treatment;
• Uncontrolled hyperglycaemia, acute attack of cholelithiasis, and susceptibility to acute pancreatitis;
• Severe or uncontrolled systemic diseases causing expected intolerance to the investigational drug as judged by the investigator;
• Toxic reactions associated with prior surgery and prior antineoplastic therapies that have not recovered and may affect the subject safety as assessed by the investigator.
• Clinically significant active bacterial, fungal or viral infections, including a positive result for hepatitis B surface antigen and HBV DNA ≥ ULN, one or more positive results for hepatitis C antibody or HIV antibody, or the presence of any uncontrolled infection.
• Use of strong CYP3A4 inducers or inhibitors or CYP3A4 substrates with a narrow therapeutic window within two weeks prior to the first dose of the investigational drug;
• Pregnant and breastfeeding female;
• Women of childbearing age who are unwilling or unable to use acceptable methods for contraception during the entire treatment period in the trial and within 6 months after the last dose of the investigational drug (women of childbearing age include: any one with menarche, and those who have not received successful artificial sterilization [hysterectomy, bilateral fallopian tube ligation, or bilateral oophorectomy] or premenopausal women); a fertile male patient who is unwilling or unable to take effective contraceptive measures, and whose partner is a woman of childbearing age;
• Being involved in other clinical studies (except for the non-interventional phase of interventional clinical study, such as survival follow-up period); less than 4 weeks from the end of the dose of other investigational drug to the first dose of the investigational drug or 5 half-lives of the previous drug, whichever is shorter;
• Any mental or cognitive disorders which may limit subjects' understanding and implementation of the informed consent form;
• Other situations, such as poor compliance, which are considered by the investigator to be not suitable for participation in the study.