Evaluation of Efficacy and Safety of Fulzerasib Sequentially Combined With Sintilimab Plus Platinum-Doublet Chemotherapy as Neoadjuvant Therapy in Patients With Resectable Non-Small Cell Lung Cancer With KRAS G12 Mutation: a Single-Arm, Phase II Clinical Trial
This is an exploratory study evaluating the efficacy and safety of neoadjuvant therapy with fulzerasib sequentially combined with sintilimab plus platinum-doublet chemotherapy in patients with resectable non-small cell lung cancer (NSCLC) harboring KRAS G12C mutation. Approximately 30 treatment-naïve patients with stage IB-IIIA (AJCC 8th edition) NSCLC and confirmed KRAS G12C mutation will be enrolled. Eligible subjects will receive 6 weeks of fulzerasib followed by a 2-week washout period, then 3 cycles (q3w) of sintilimab plus investigator's choice of platinum-doublet chemotherapy. An end-of-treatment visit will be performed within 7 days after the last dose of neoadjuvant therapy.
• Sign the Informed Consent Form (ICF) and be able to comply with the visit and related procedures as stipulated in the protocol.
• Be male or female, aged ≥18 years old.
• Histologically or cytologically confirmed primary non-small cell lung cancer (NSCLC).
• Clinical stage IB to IIIA disease, according to the 8th edition of the TNM classification for lung cancer as defined by the International Association for the Study of Lung Cancer (IASLC) and the American Joint Committee on Cancer (AJCC).
• All subjects must have a written test report before enrollment to prove the presence of KRAS G12C mutation; and must have no sensitive mutations of Epidermal Growth Factor Receptor (EGFR), Anaplastic Lymphoma Kinase (ALK).
• The patient is deemed by a thoracic surgeon to be a candidate for curative resection (R0 resection) and has adequate pulmonary function to undergo the planned pulmonary resection.
• Have at least one measurable lesion according to RECIST 1.1 criteria.
• Have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 or 1.
• Have not received any systemic anti-tumor treatment for locally advanced or metastatic NSCLC before.
⁃ Have adequate organ and bone marrow function (subjects who have received any cell or growth factor therapy within 2 weeks before the first administration of the study drug should be excluded), defined as follows:
‣ 1\) Blood routine: Absolute neutrophil count (ANC) ≥1.5×109/L or within the normal range; platelet (PLT) count ≥100×109/L; hemoglobin (HGB) content ≥9.0 g/dL.
‣ 2\) Liver function: Serum total bilirubin (TBIL) ≤1.5×Upper Limit of Normal Value (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN.
‣ 3\) Renal function: Serum creatinine (Cr) ≤1.5×ULN or clearance of creatinine (CCr) ≥50 mL/min, calculated by the Cockcroft-Gault formula (using actual body weight); urine routine test shows urine protein \<2+; for subjects with urine protein ≥2+ at baseline as detected by urine test strips, a 24-hour urine collection should be performed and the protein content in 24-hour urine should be \<1 g (if both methods are used, the value obtained from 24-hour urine collection will be used to determine eligibility).
‣ 4\) Coagulation function: Activated Partial Thromboplastin Time (APTT) ≤ 1.5×ULN and International Normalized Ratio (INR) ≤ 1.5; 11. Female subjects of childbearing age or male subjects whose partners are of childbearing age must take effective contraceptive measures throughout the treatment period and for 180 days after the treatment.
• Female subjects have evidence of postmenopausal status, or the urine or serum pregnancy test results of premenopausal female subjects are negative.