An Apen-label, Multicenter Phase II Study to Evaluate the Efficacy and Safety of BEBT-109 in Patients With EGFR Exon 20 Insertion Mutations in Locally Advanced or Metastatic Non-Small Cell Lung Cancer
This study is an open-label, multicenter Phase II trial, planning to enroll 200 subjects, using BEBT-109 capsules as monotherapy, aimed at evaluating the efficacy and safety of BEBT-109 capsules in subjects with Epidermal Growth Factor Receptor (EGFR) exon 20 insertion mutations in locally advanced or metastatic Non-Small Cell Lung Cancer （NSCLC）.
• Subjects who have been fully informed and are willing to sign the informed consent form.
• Age of at least 18 years, with no gender restrictions.
• According to the 8th edition of the American Joint Committee on Cancer (AJCC) lung cancer Tumor Node Metastasis (TNM) staging criteria: histologically or cytologically confirmed locally advanced (stages IIIB or IIIC, and deemed unsuitable for surgery or radiotherapy by the investigator) or metastatic (stage IV) NSCLC.
• Written test reports confirm the occurrence of EGFR exon 20 insertion mutations.
• Cohort 1 includes NSCLC patients who have failed or are intolerant to at least one systemic chemotherapy (defined as having undergone at least one platinum-based chemotherapy regimen or other chemotherapy regimen) and have not received third-generation EGFR TKI treatment; Cohort 2 includes NSCLC patients who have failed or are intolerant to at least one systemic chemotherapy (defined as having undergone at least one platinum-based chemotherapy regimen or other chemotherapy regimen) and have experienced Progressive Disease after receiving standard doses of third-generation EGFR TKI (such as osimertinib 80 mg once daily, or savolitinib 80 mg once daily, or alectinib 110 mg once daily, etc.).
• Eastern Cooperative Oncology Group (ECOG) score of 0-2, with no decline in physical performance in the past two weeks, and an expected survival of at least 12 weeks.
• Subjects must have at least one measurable lesion according to Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 criteria.
• Laboratory tests indicate that subjects have adequate organ function: including: a. Absolute neutrophil count (ANC) ≥1.5×10\^9/L; platelet count (PLT) ≥100×10\^9/L; hemoglobin (HGB) ≥80g/L; b. Serum total bilirubin (TBIL) ≤1.5 times the upper limit of normal (ULN), aspartate transaminase (AST) and alanine aminotransferase (ALT) ≤2.5 times ULN (for those with liver metastasis, total bilirubin ≤3 times ULN, AST and ALT ≤5 times ULN are allowed); c. Creatinine ≤1.5 times ULN, when creatinine \>1.5 times ULN, creatinine clearance must be confirmed, and creatinine clearance must be ≥45 ml/min (actual value, or calculated by the Cockcroft-Gault formula); d. Activated partial thromboplastin time (APTT) ≤1.5 times ULN, prothrombin time (PT) ≤1.5 times ULN, international normalized ratio (INR) ≤1.5 times ULN.
• If the subject is a female with childbearing potential, she must use adequate contraceptive measures (such as condoms), must not breastfeed, and must have a negative blood pregnancy test before dosing.
⁃ male subjects must be willing to use barrier contraceptive measures during the study period, i.e., condoms.