Mechanism of Enhanced Efficacy of Ivonescimab in Neoadjuvant Therapy for Non-Small Cell Lung Cancer

March 10, 2026 updated by: Yang Fan, MD, Peking University People's Hospital

Mechanisms of Enhanced Efficacy of Ivonescimab in Neoadjuvant Therapy for Non-Small Cell Lung Cancer

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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.

Study Type

Observational

Enrollment (Estimated)

80

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Beijing Municipality
      • Beijing, Beijing Municipality, China, 100044
        • Peking University People's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

The study primarily involves patients with small cell lung cancer who require neoadjuvant immunotherapy.

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Ivonescimab neoadjuvant therapy group
Patients in this group will receive ivonescimab as neoadjuvant therapy
Drug: Ivonescimab
Patients in the experimental group will receive ivonescimab as neoadjuvant therapy.
PD-1 inhibitors neoadjuvant therapy group
Patients in this group will receive other PD-1 inhibitors as neoadjuvant therapy
Drug: PD-1 Inhibitors
Patients in the positive control group will receive PD-1 inhibitors monotherapy as neoadjuvant treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pathological Complete Response (pCR
Time Frame: 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.
At surgery (typically 3-6 months post-treatment initiation)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Major Pathological Response (MPR)
Time Frame: 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.
At surgery (typically 3-6 months post-treatment initiation)
Objective Response Rate (ORR)
Time Frame: 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.
After two cycles or four cycles of neoadjuvant therapy (each cycle is 21 days).
Immune-Related Adverse Event (irAE) Incidence
Time Frame: 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).
Periprocedural and up to 6 months post-treatment.
Overall Survival (OS)
Time Frame: Through study completion, an average of 2 years.
Time from randomization to death from any cause.
Through study completion, an average of 2 years.
MRD (minimal residual disease) dynamics after neoadjuvant immunotherapy
Time Frame: 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.
Periprocedural and every three to six months post-treatment (up to three years).
Event-free Survival (EFS)
Time Frame: 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.
Through study completion, an average of 2 years.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Peking University People's Hospital

Investigators

  • Principal Investigator: Fan Yang, Peking University People's Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 1, 2025

Primary Completion (Estimated)

December 21, 2026

Study Completion (Estimated)

October 30, 2027

Study Registration Dates

First Submitted

January 13, 2026

First Submitted That Met QC Criteria

January 13, 2026

First Posted (Actual)

January 22, 2026

Study Record Updates

Last Update Posted (Actual)

March 12, 2026

Last Update Submitted That Met QC Criteria

March 10, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BRWEP2024W034080205

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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