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.
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.
Study Type
OBSERVATIONAL
Enrollment
80
Patients in the experimental group will receive ivonescimab as neoadjuvant therapy.
Patients in the positive control group will receive PD-1 inhibitors monotherapy as neoadjuvant treatment.
Peking University People's Hospital
Beijing, Beijing Municipality, China
RECRUITINGPathological Complete Response (pCR
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.
Time frame: At surgery (typically 3-6 months post-treatment initiation)
Major Pathological Response (MPR)
Major Pathologic Response (MPR) is defined as the presence of ≤10% residual viable tumor cells in both the primary lung tumor site and sampled regional lymph nodes after neoadjuvant immunotherapy, confirmed through systematic pathological examination of the surgical specimen.
Time frame: At surgery (typically 3-6 months post-treatment initiation)
Objective Response Rate (ORR)
ORR is defined as the proportion of patients achieving either a complete response (CR; disappearance of all target lesions) or partial response (PR; ≥30% reduction in the sum of target lesion diameters) during or after neoadjuvant immunotherapy, as assessed by serial imaging (CT/PET-CT) using iRECIST criteria.
Time frame: After two cycles or four cycles of neoadjuvant therapy (each cycle is 21 days).
Event-free Survival (EFS)
Time from randomization to the occurrence of any of the following events: disease progression, recurrence, discontinuation of treatment due to toxicity, initiation of new anticancer therapy, or death from any cause.
Time frame: Through study completion, an average of 2 years.
Overall Survival (OS)
Time from randomization to death from any cause.
Time frame: Through study completion, an average of 2 years.
MRD (minimal residual disease) dynamics after neoadjuvant immunotherapy
Postoperative dynamics of ctDNA-based MRD and timely detection of recurrence or metastasis in lung cancer patients receiving neoadjuvant immunotherapy.
Time frame: Periprocedural and every three to six months post-treatment (up to three years).
Immune-Related Adverse Event (irAE) Incidence
Frequency and severity of adverse events (e.g., rash, colitis) related to immunotherapy, graded using standardized criteria like CTCAE (Common Terminology Criteria for Adverse Events).
Time frame: Periprocedural and up to 6 months post-treatment.
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