Adjuvant Immune Checkpoint Inhibitor Versus Observation in Patients With Completely Resected Non-Small Cell Lung Cancer at High Risk of Recurrence After Neoadjuvant Immunochemotherapy: A Multicenter, Randomized, Open-Label, Phase II Trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 100
- 试验地点
- 2
- 主要终点
- 18-Month Disease-Free Survival Rate
研究概览
简要总结
This multicenter, randomized, open-label, phase II trial is designed to evaluate the efficacy and safety of adjuvant sintilimab in patients with completely resected non-small cell lung cancer who remain at high risk of recurrence after neoadjuvant immunochemotherapy.
Approximately 100 eligible participants will be randomly assigned in a 1:1 ratio to receive either adjuvant sintilimab or observation. Participants assigned to the experimental arm will receive sintilimab at a dose of 200 mg intravenously every 4 weeks for up to 1 year, unless disease recurrence or progression, unacceptable toxicity, withdrawal of consent, or another protocol-defined discontinuation criterion occurs.
The primary outcome is the 18-month disease-free survival rate. Secondary outcomes include disease-free survival, overall survival, and safety. Peripheral blood and tumor tissue samples will also be collected for exploratory analyses of ctDNA, antitumor immune responses, and tumor immune microenvironment biomarkers.
详细描述
Although perioperative immune checkpoint inhibitor therapy has improved outcomes in patients with resectable non-small cell lung cancer, the contribution of postoperative immunotherapy following neoadjuvant immunochemotherapy remains uncertain. In particular, it is unclear whether patients with residual high-risk clinicopathologic or molecular features after complete resection derive additional benefit from adjuvant immune checkpoint inhibition.
This prospective, multicenter, randomized, open-label, phase II trial will enroll patients with completely resected non-small cell lung cancer who previously received 2 to 4 cycles of neoadjuvant immune checkpoint inhibitor therapy combined with chemotherapy and who have at least one protocol-defined high-risk feature for postoperative recurrence.
High-risk features include pathologic lymph-node involvement, postoperative pathologic T2 or higher disease, failure to achieve a major pathologic response, pleural invasion, intravascular tumor emboli, high-risk histologic components, or detectable molecular residual disease.
Eligible participants will be randomly assigned in a 1:1 ratio to receive adjuvant sintilimab or observation. Sintilimab will be administered intravenously at a dose of 200 mg every 4 weeks for up to 1 year. Participants in both groups will undergo protocol-defined surveillance for disease recurrence, survival, and adverse events.
The primary objective is to compare the 18-month disease-free survival rate between the two groups. Secondary objectives include the evaluation of disease-free survival, overall survival, and safety. Exploratory objectives include assessment of peripheral and tumor-associated immune biomarkers, T-cell responses, molecular residual disease dynamics, and their associations with clinical outcomes.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female participants aged 18 to 75 years.
- •Histologically or cytologically confirmed non-small cell lung cancer.
- •Completion of 2 to 4 cycles of neoadjuvant immune checkpoint inhibitor therapy combined with chemotherapy, followed by complete (R0) surgical resection.
- •At least one of the following protocol-defined high-risk features for postoperative recurrence:
- •Pathologic lymph-node involvement;
- •Postoperative pathologic T2 or higher disease;
- •Failure to achieve a major pathologic response, defined as more than 10% residual viable tumor cells in the primary tumor;
- •Pleural invasion;
- •Intravascular tumor emboli;
- •High-risk histologic components, including solid, micropapillary, or adenosquamous components;
- •Detectable molecular residual disease.
- •For participants with lung adenocarcinoma, absence of sensitizing EGFR mutations and ALK rearrangements. Molecular testing is not mandatory for participants with squamous cell carcinoma according to the current protocol.
- •Eastern Cooperative Oncology Group performance status of 0 or
- •Adequate organ function within 7 days before randomization, as demonstrated by all of the following:
- •Hemoglobin of at least 90 g/L;
- •Absolute neutrophil count of at least 1.5 × 10^9/L;
- •Platelet count of at least 75 × 10^9/L;
- •Total bilirubin no greater than 1.5 times the upper limit of normal;
- •Alanine aminotransferase and aspartate aminotransferase no greater than 2.5 times the upper limit of normal;
- •Serum creatinine no greater than 1.5 times the upper limit of normal or creatinine clearance of at least 60 mL/min;
- •Left ventricular ejection fraction of at least 50%;
- •International normalized ratio or prothrombin time no greater than 1.5 times the upper limit of normal.
- •Women of childbearing potential must have a negative pregnancy test within 7 days before the first dose and must agree to use effective contraception during the study and for 3 months after the last dose of study treatment. Male participants with partners of childbearing potential must agree to use effective contraception during the study and for 8 weeks after the last dose.
- •Ability to understand the study requirements, willingness to provide written informed consent, and ability to comply with study treatment and follow-up procedures.
排除标准
- •Small cell lung cancer or non-small cell lung cancer containing a small cell carcinoma component.
- •Incomplete resection, including R1 or R2 resection, or salvage surgery.
- •Clinically significant malnutrition as determined by the investigator.
- •A history of clinically significant immune-related adverse events during prior treatment, including grade 3 or higher immune-mediated pneumonitis, myocarditis, or another serious immune-related adverse event that, in the investigator's judgment, makes further immune checkpoint inhibitor therapy unsafe.
- •Signs, symptoms, or a known history of clinically significant interstitial lung disease.
- •Any severe or uncontrolled concurrent medical condition, including:
- •Inadequately controlled hypertension;
- •Grade 2 or higher myocardial ischemia, myocardial infarction, clinically significant arrhythmia, corrected QT interval of at least 480 milliseconds, or New York Heart Association class II or higher heart failure;
- •Active or uncontrolled infection of grade 2 or higher;
- •Decompensated liver disease, active hepatitis, or chronic viral hepatitis requiring antiviral therapy;
- •Renal failure requiring hemodialysis or peritoneal dialysis;
- •Known human immunodeficiency virus infection, another acquired or congenital immunodeficiency disorder, or a history of organ transplantation;
- •Poorly controlled diabetes mellitus, defined as fasting blood glucose greater than 10 mmol/L;
- •Urine protein of 2+ or greater with a 24-hour urinary protein level greater than 1.0 g;
- •Clinically significant coagulation abnormalities or an increased risk of bleeding;
- •A seizure disorder requiring treatment.
- •A concurrent active malignancy, except for malignancies specifically permitted by the final protocol.
- •An active autoimmune disease or another immune-mediated disease requiring systemic treatment.
- •Long-term treatment with systemic immunosuppressive therapy or systemic corticosteroids, except for protocol-permitted physiologic replacement therapy.
- •An active psychiatric disorder, cognitive impairment, or another condition that would prevent provision of informed consent or adherence to study treatment and follow-up.
- •Any other condition that, in the investigator's judgment, makes the participant unsuitable for the study.
研究组 & 干预措施
Observation
Participants will receive no protocol-mandated postoperative immune checkpoint inhibitor therapy and will undergo standard clinical and radiographic surveillance according to the study protocol.
Adjuvant Sintilimab
Participants will receive sintilimab 200 mg by intravenous infusion once every 4 weeks for up to 1 year. Treatment will continue until completion of the planned treatment period, documented disease recurrence or progression, unacceptable toxicity, withdrawal of consent, or another protocol-defined discontinuation criterion.
干预措施: Sintilimab (Drug)
结局指标
主要结局
18-Month Disease-Free Survival Rate
时间窗: At 18 months after definitive surgery
The Kaplan-Meier estimated proportion of participants who are alive and free from local recurrence, regional recurrence, distant metastasis, or death from any cause at 18 months after definitive surgery. Participants without a documented disease-free survival event will be censored at the date of their last disease assessment.
次要结局
- Overall Survival(From the date of initial histopathologic diagnosis until death from any cause, assessed up to 36 months.)
- Incidence of Adverse Events(From informed consent through 30 days after completion or discontinuation of the protocol-defined treatment，up to approximately 1 years.)
- Disease-Free Survival(From the date of definitive surgery until the first documented disease recurrence or death from any cause, assessed up to 36 months.)
研究者
Zhen-Yu Ding
Clinical Professor
Sichuan University