A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of CFT8919 Capsules in Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC).
The goal of this clinical trial is to evaluate the safety, tolerability, pharmacokinetics, and antitumor activity of CFT8919 capsules in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) carrying EGFR mutations. The main questions it aims to answer are: * What is the maximum tolerated dose (MTD) of CFT8919? * Does CFT8919 demonstrate antitumor activity in these patients? Participants will: * Take CFT8919 capsules at different doses. * Undergo regular assessments for safety, pharmacokinetics, and tumor response. Researchers will compare different dose levels to determine the best balance between safety and efficacy.
• Dose-Escalation and Dose-Expansion Phases: Patients with histologically or cytologically confirmed locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring the EGFR-L858R mutation, who have failed standard treatment (disease progression or intolerance), lack standard treatment options, or are deemed unsuitable for standard treatment by the investigator, or have refused standard treatment.
• Cohort-Expansion Phase: In addition to the above criteria, the following must also be met:
‣ Cohort A: Patients with locally advanced or metastatic NSCLC harboring the EGFR-L858R mutation who have experienced disease progression after third-generation EGFR-TKI treatment and carry secondary EGFR mutations (such as C797S, L718Q, G724S, S768I, etc.).
⁃ Cohort B: Patients with locally advanced or metastatic NSCLC harboring the EGFR-L858R mutation who have failed standard treatment or are unsuitable for or have refused standard treatment (patients with secondary EGFR mutations are prioritized for Cohort A).
• • Dose-Escalation Phase requires evaluable lesions, while Dose-Expansion and Cohort-Expansion Phases require measurable lesions as defined by RECIST V1.1.
• • Age ≥18 years, no gender restrictions.
• • Expected survival ≥12 weeks.
• • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• • Adequate organ function, meeting the following criteria:
‣ Hematologic: Absolute neutrophil count (ANC) ≥1.5 × 10⁹/L (1500/mm³), platelets ≥100 × 10⁹/L, hemoglobin ≥9 g/dL (90 g/L) without transfusion or hematopoietic growth factors within 14 days prior to screening.
⁃ Coagulation: International normalized ratio (INR) and activated partial thromboplastin time (APTT) ≤1.5 × the upper limit of normal (ULN).
⁃ Liver: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN, or ≤5.0 × ULN in the presence of liver metastases; total bilirubin (TBIL) ≤1.5 × ULN, or ≤3.0 × ULN in the presence of liver metastases or known Gilbert\'s syndrome (unconjugated hyperbilirubinemia).
⁃ Kidney: Serum creatinine (Scr) ≤1.5 × ULN, or for patients with Scr \>1.5 × ULN, creatinine clearance (Ccr) ≥50 mL/min (calculated using the Cockcroft-Gault formula); urine protein ≤1+, or if ≥2+, 24-hour urine protein quantification showing \<1 g.
• • Toxicity from prior anti-tumor treatments must have resolved to CTCAE grade ≤1 (except for toxicities that, in the investigator\'s judgment, are long-lasting and non-recoverable but pose no safety risk and are ≤2 in grade).
• • Patients must have been previously diagnosed with the EGFR-L858R mutation via local testing. In the Dose-Escalation and Dose-Expansion Phases, patients who progressed on prior EGFR-TKI treatment must provide the genetic mutation results from their most recent EGFR-TKI treatment. For Cohort A patients, progression on third-generation EGFR-TKI treatment must have confirmed the presence of secondary EGFR mutations (e.g., C797S, L718Q, G724S, S768I) via tissue or blood tests.
⁃ • Patients must be willing to provide blood samples and optionally provide tissue samples for exploratory biomarker research.
⁃ • Non-breastfeeding women of childbearing potential must have a negative serum or urine pregnancy test within 7 days before starting study treatment, and all enrolled patients must agree to use medically accepted contraception for 1 month prior to treatment, during the entire treatment period, and for 3 months after completing treatment.
⁃ • Signed informed consent form.