Mechanisms of Enhanced Efficacy of Ivonescimab in Neoadjuvant Therapy for Non-Small Cell Lung Cancer
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Pathological Complete Response (pCR
研究概览
简要总结
This is an exploratory clinical study focusing on the neoadjuvant treatment of non-small cell lung cancer (NSCLC). The study primarily aims to compare the efficacy and safety of Ivonescimab, a novel PD-1/VEGF bispecific antibody, with those of conventional PD-1 inhibitors. Beyond evaluating its direct therapeutic benefits, this research also seeks to elucidate the potential mechanisms underlying the enhanced efficacy of Ivonescimab. Additionally, the study will conduct secondary exploratory analyses, including the identification and validation of predictive and prognostic biomarkers, as well as multi-omics profiling to investigate the molecular mechanisms of action. Collectively, these efforts aim to provide comprehensive experimental data to support the rational clinical application of Ivonescimab and the development of precision medicine strategies for NSCLC.
详细描述
Lung cancer is one of the leading causes of cancer-related deaths in China and worldwide, imposing a significant societal burden. Although comprehensive treatment strategies centered around surgery have improved patient prognosis, and perioperative immunotherapy has profoundly reshaped the therapeutic landscape, this field still faces substantial knowledge gaps and key challenges.
This study focuses on Ivonescimab, a first-in-class PD-1/VEGF bispecific antibody. Ivonescimab simultaneously blocks PD-1 to reactivate antitumor immune response by releasing T-cell inhibition and inhibits VEGF to suppress tumor angiogenesis while modulating the immunosuppressive tumor microenvironment. The primary objectives of this research are to evaluate the efficacy and safety of Ivonescimab compared with conventional immunotherapy and to investigate its potential mechanisms of action, thereby providing scientific evidence to support its clinical application.The secondary objectives are to identify and validate potential predictive and prognostic biomarkers associated with the clinical efficacy and safety of Ivonescimab, and to perform multi-omics analyses (including genomics, transcriptomics, proteomics, and metabolomics) to explore the underlying molecular mechanisms of Ivonescimab in regulating antitumor immune response, remodeling tumor angiogenesis, and modulating the tumor microenvironment, so as to lay a theoretical foundation for the precise application of Ivonescimab and the development of combined therapeutic strategies.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with non-small cell lung cancer (Stage IB-IIIB) who require radical surgery following neoadjuvant therapy.
排除标准
- •Histology of other malignant tumors, including concurrent malignant tumors of other organ systems;
- •Unresectable advanced disease (Stage IV) or locally advanced unresectable (Stage IIIC);
- •Pregnancy or lactation;
- •Insufficient sample quality;
- •Severe organ dysfunction (e.g. cardiac or renal insufficiency);
- •Other judgments by the Investigator that the patient should not participate in the study.
研究组 & 干预措施
Ivonescimab neoadjuvant therapy group
Patients in this group will receive ivonescimab as neoadjuvant therapy
干预措施: Ivonescimab (Drug)
PD-1 inhibitors neoadjuvant therapy group
Patients in this group will receive other PD-1 inhibitors as neoadjuvant therapy
干预措施: PD-1 Inhibitors (Drug)
结局指标
主要结局
Pathological Complete Response (pCR
时间窗: At surgery (typically 3-6 months post-treatment initiation)
Pathologic Complete Response (pCR) is defined as the absence of residual tumor in both the primary lung tumor site and all sampled regional lymph nodes after neoadjuvant immunotherapy, confirmed through systematic pathological examination of the surgical specimen.
次要结局
- Major Pathological Response (MPR)(At surgery (typically 3-6 months post-treatment initiation))
- Objective Response Rate (ORR)(After two cycles or four cycles of neoadjuvant therapy (each cycle is 21 days).)
- Event-free Survival (EFS)(Through study completion, an average of 2 years.)
- Overall Survival (OS)(Through study completion, an average of 2 years.)
- MRD (minimal residual disease) dynamics after neoadjuvant immunotherapy(Periprocedural and every three to six months post-treatment (up to three years).)
- Immune-Related Adverse Event (irAE) Incidence(Periprocedural and up to 6 months post-treatment.)
研究者
Yang Fan, MD
Vice President
Peking University People's Hospital