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

Prior treatment

• 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.
• 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.
• 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;
• 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;

Other illness

• 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;
• History of active pneumonia or clinically significant interstitial pneumonia, or radiation or drug-induced lung disorder with treatment needs;
• Cardiac insufficiency;
• Uncontrolled hypertension after drug treatment;
• Any mental or cognitive disorders which may limit subjects' understanding and implementation of the informed consent form;

Lab values

• 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;
• 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.

Other

• Abnormal gastrointestinal function that affect absorption within the past 6 months;
• Uncontrolled hyperglycaemia, acute attack of cholelithiasis, and susceptibility to acute pancreatitis;
• Pregnant and breastfeeding female;
• Other situations, such as poor compliance, which are considered by the investigator to be not suitable for participation in the study.

• 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.