A Phase I Study of CFT8919 in Patients With Advanced NSCLC

Exclusion Criteria

• •1. Prior or ongoing treatment with EGFR-L858R-targeted PROTAC therapies.
• •2. Less than 5 half-lives or 4 weeks (whichever is shorter) since the last anti-tumor treatment before the first dose of study drug; less than 6 weeks since the last treatment with nitrosoureas or mitomycin C; less than 1 week since the last anti-tumor herbal treatment.
• •3. Patients who underwent major surgery (as defined by the investigator) or experienced significant trauma within 4 weeks before the first dose of study drug; patients who received radiation therapy within 4 weeks prior to the first dose, except for palliative radiation (e.g., for bone metastases to control pain) that is unlikely to affect bone marrow function, which may allow inclusion 2 weeks post-radiation.
• •4. Patients with unstable central nervous system (CNS) metastases (those who have received treatment for brain metastases, have stable brain lesions, and have discontinued corticosteroids, anticonvulsants, or mannitol treatment for ≥2 weeks before the first dose may be considered for inclusion); patients with leptomeningeal metastases or spinal cord compression.
• •5. History of other primary malignancies within the past 3 years, except for malignancies that have been treated curatively with no known active disease and a low risk of recurrence, or adequately treated non-melanoma skin cancers, cervical carcinoma in situ, or papillary thyroid carcinoma.
• •6. Clinically significant cardiovascular diseases, including but not limited to:
• •* a) Unstable angina, acute myocardial infarction, or New York Heart Association (NYHA) class II-IV heart failure;
• •* b) Ventricular arrhythmias or conduction disorders requiring clinical intervention (e.g., complete left bundle branch block, third-degree atrioventricular \[AV\] block, or second-degree AV block);
• •* c) Uncontrolled atrial fibrillation or atrial flutter;
• •* d) Prolonged QTcF interval (resting mean QTcF \>450 msec for men or \>470 msec for women);
• •* e) Left ventricular ejection fraction (LVEF) \<50% on echocardiography;
• •* f) Hypertension not controlled with medication.
• •7. • History of interstitial lung disease (ILD) or non-infectious pneumonitis.
• •8. • Adrenal insufficiency.
• •9. • Use of proton pump inhibitors, strong CYP3A4 inhibitors or inducers, or P-glycoprotein inhibitors or inducers within 7 days before the first dose.
• •10. • History of chronic diarrhea or diseases causing chronic diarrhea, such as Crohn\'s disease or irritable bowel syndrome, or any condition that might affect drug absorption (e.g., continuous diarrhea \>CTCAE grade 1 within 1 week prior to the first dose).
• •11. • Known severe hypersensitivity to the study drug or any of its excipients.
• •12. • History of deep vein thrombosis, pulmonary embolism, or any other serious thromboembolic events within 6 months before the first dose, except for catheter-related or superficial venous thrombosis, or lacunar infarcts.
• •13. • Clinically significant gastrointestinal bleeding or hemoptysis within 3 months before the first dose, or any other significant bleeding history (e.g., pulmonary hemorrhage).
• •14. • Clinically significant third-space fluid accumulation (e.g., uncontrolled ascites, pleural effusion, or pericardial effusion requiring repeated drainage).
• •15. • Receipt of autologous transplantation within 3 months or allogeneic organ or stem cell transplantation within 6 months prior to the first dose.
• •16. • Active hepatitis B virus (HBV) infection (screening positive for HBsAg or anti-HBc, and HBV DNA levels above the detection limit; patients with stable disease for at least 4 weeks after antiviral therapy may be included), active hepatitis C virus (HCV) infection (positive HCV antibodies and detectable HCV RNA), human immunodeficiency virus (HIV) infection, or active syphilis infection.
• •17. • Active infection requiring systemic treatment within 1 week before the first dose.
• •18. • History of substance abuse or any condition that, in the investigator\'s judgment, may interfere with study participation or assessment of study results, or any unstable condition that may compromise patient safety or compliance.