Immunotherapy, Neoadjuvant Therapy, Non-Small Cell Lung Cancer, PD-1 Inhibitors
Conditions
Keywords
Neoajuvant therapy, Ivonescimab, Non-Small Cell Lung Cancer
Brief summary
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.
Detailed description
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.
Interventions
DRUGIvonescimab
Patients in the experimental group will receive ivonescimab as neoadjuvant therapy.
DRUGPD-1 Inhibitors
Patients in the positive control group will receive PD-1 inhibitors monotherapy as neoadjuvant treatment.
Sponsors
Peking University People's Hospital
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
Patients with non-small cell lung cancer (Stage IB-IIIB) who require radical surgery following neoadjuvant therapy.
Exclusion criteria
1. Histology of other malignant tumors, including concurrent malignant tumors of other organ systems; 2. Unresectable advanced disease (Stage IV) or locally advanced unresectable (Stage IIIC); 3. Pregnancy or lactation; 4. Insufficient sample quality; 5. Severe organ dysfunction (e.g. cardiac or renal insufficiency); 6. Other judgments by the Investigator that the patient should not participate in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pathological Complete Response (pCR | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Major Pathological Response (MPR) | At surgery (typically 3-6 months post-treatment initiation) | 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. |
| Objective Response Rate (ORR) | After two cycles or four cycles of neoadjuvant therapy (each cycle is 21 days). | 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. |
| Event-free Survival (EFS) | Through study completion, an average of 2 years. | 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. |
| Overall Survival (OS) | Through study completion, an average of 2 years. | Time from randomization to death from any cause. |
| MRD (minimal residual disease) dynamics after neoadjuvant immunotherapy | Periprocedural and every three to six months post-treatment (up to three years). | Postoperative dynamics of ctDNA-based MRD and timely detection of recurrence or metastasis in lung cancer patients receiving neoadjuvant immunotherapy. |
| Immune-Related Adverse Event (irAE) Incidence | Periprocedural and up to 6 months post-treatment. | 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). |
Countries
China
Contacts
CONTACTHao Li
CONTACTHuiming Han
PRINCIPAL_INVESTIGATORFan Yang
Peking University People's Hospital
Outcome results
None listed