Adaptive Adjuvant Sintilimab Therapy Guided by MRD in II-IIIB Stage NSCLC Patients With Non-pCR Pathological Response After Neoadjuvant Immunotherapy Combined With Chemotherapy: a Prospective, Multi-center, Single-arm, Phase II Trial
This is a multicenter, prospective, open-label Phase II study designed to evaluate the safety and efficacy of adjuvant sintilimab therapy guided by minimal residual disease (MRD) in patients with Stage II-IIIB non-small cell lung cancer (NSCLC) who have not achieved a pathological complete response (non-pCR) after neoadjuvant immunotherapy combined with chemotherapy. The study is being conducted at the Third People's Hospital of Chengdu and the Guangdong Provincial People's Hospital.
• Signed written informed consent prior to the initiation of any trial-related procedures.
• Male or female aged ≥18 years and ≤75 years.
• Histologically or cytologically confirmed non-small cell lung cancer (NSCLC).
• Received 3-4 cycles of neoadjuvant immunotherapy (PD-1 inhibitor) combined with chemotherapy.
• Underwent radical surgical treatment (R0), with surgical procedures including lobectomy or sleeve lobectomy. All gross tumors must be completely resected at the end of surgery, and all surgical margins of the resected tumors must be negative. Systemic lymph node dissection is required.
• Clinical stage II, IIIA, or IIIB (limited to resectable N2) according to the AJCC 8th edition TNM classification for lung cancer. Resectable N2 refers to non-massive (defined as short-axis diameter \<3 cm), discrete, or single-station N2 involvement. If clinically suspected of N2 or N3, pathological confirmation is recommended whenever feasible.
• Patients with pathological response assessment of 1%-90% residual viable tumor (RVT).
• No EGFR mutations, ROS1 fusions, ALK fusions, or RET fusions. Other potentially targetable driver gene alterations will be determined in consultation with the sponsor.
• No prior anti-tumor treatment other than PD-1 inhibitors and chemotherapy before radical surgery for lung cancer.
⁃ Completed radical surgery for lung cancer 4-12 weeks prior to study enrollment, with pathological confirmation of R0 resection and radiological evidence of no residual tumor foci 1 month after radical surgery.
⁃ Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
⁃ Life expectancy \>6 months.
⁃ Adequate organ function:
‣ 1\. Absolute neutrophil count (ANC) ≥1.5×10\^9/L without the use of granulocyte colony-stimulating factor within the past 14 days.
‣ 2\. Platelets ≥100×10\^9/L without transfusion within the past 14 days. 3. Hemoglobin \>9 g/dL without transfusion or use of erythropoiesis-stimulating agents within the past 14 days.
‣ 4\. Total bilirubin ≤1.5× upper limit of normal (ULN). 5. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5×ULN (subjects with liver metastases are allowed to have ALT or AST ≤5×ULN).
‣ 6\. Serum creatinine ≤1.5×ULN and creatinine clearance (calculated using the Cockcroft-Gault formula) ≥60 ml/min.
‣ 7\. Good coagulation function, defined as international normalized ratio (INR) or prothrombin time (PT) ≤1.5×ULN.
‣ 8\. Normal thyroid function, defined as thyroid-stimulating hormone (TSH) within the normal range. Subjects with baseline TSH outside the normal range are eligible if total T3 (or free T3) and free T4 are within the normal range.
‣ 9\. Cardiac enzyme profile within the normal range (subjects with isolated laboratory abnormalities deemed not clinically significant by the investigator are also eligible).
‣ 14\. For female subjects of childbearing potential, a negative urine or serum pregnancy test must be obtained within 3 days prior to the first administration of the study drug (Day 1 of Cycle 1). If the urine pregnancy test result is inconclusive, a serum pregnancy test is required. Postmenopausal women are defined as those who have been amenorrheic for at least 1 year, or those who have undergone surgical sterilization or hysterectomy.
‣ 15\. All subjects (regardless of gender) at risk of conception must use contraception with a failure rate of less than 1% per year throughout the treatment period until 120 days after the last administration of the study drug (or 180 days after the last administration of chemotherapy).
‣ 16\. Provide samples for MRD assessment (surgical tissue + blood).