Efficacy of Anti-CTLA-4 Antibody Combined With Sintilimab and Chemotherapy as Neoadjuvant Therapy for Resectable Stage II-III Non-Small Cell Lung Cancer: A Phase II, Single-Arm Clinical Study
This study aims to evaluate the major pathologic response (MPR) rate of neoadjuvant therapy with sintilimab (PD-1 inhibitor) + IBI310 (anti-CTLA-4 antibody) + chemotherapy, and to assess the efficacy of this treatment strategy in patients with PD-L1-negative stage II - IIIB (excluding N3) NSCLC (according to AJCC 9th) scheduled for surgery.
• The patient shall sign the informed consent.
• Age ≥ 18 years.
• Histologically or cytologically confirmed non-small-cell lung cancer (NSCLC).
• No prior anticancer therapy, including (but not limited to) chemotherapy, immunotherapy or radiotherapy. Traditional Chinese medicine given for anticancer intent is permitted provided it was discontinued ≥ 2 weeks before first dose.
• Investigator-assessed resectable Stage II-IIIB (N3 excluded) NSCLC per AJCC 9th.
• Non-squamous NSCLC: no EGFR mutation, ALK rearrangement or any other driver mutation with an approved targeted agent. Squamous NSCLC: no known EGFR mutation, ALK rearrangement or other actionable driver mutation.
• PD-L1 expression negative (22C3 or E1L3N).
• ECOG performance status 0 or 1.
• Adequate organ function within 7 days before first dose:
‣ Haemoglobin ≥ 90 g/L (no transfusion within 28 days)
⁃ Absolute neutrophil count ≥ 1.5 × 10⁹/L
⁃ Platelet count ≥ 100 × 10⁹/L (no platelet transfusion or IL-11 within 14 days)
⁃ Creatinine clearance ≥ 60 mL/min (Cockcroft-Gault)
⁃ Total bilirubin ≤ 1.5 × ULN (≤ 2.5 × ULN in Gilbert's syndrome or hepatic metastases)
⁃ ALT and AST ≤ 3 × ULN
⁃ INR or aPTT ≤ 1.5 × ULN
⁃ FEV\> 2L, FEV1\> 1L, FEV1/FVC ≥ 70%, DLCO ≥ 70% predicted; or Investigator determination that pulmonary reserve is adequate for planned surgery.
⁃ Fertile female must have a negative serum pregnancy test within 7 days before first dose.
⁃ Fertile female and male patients with female partners of childbearing potential must use a highly effective contraceptive method (annual failure rate \< 1 %) from 7 days before first dose until 24 weeks after the last dose.