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

NCT07359040 | Recruiting DMC

• 1 other identifier: BRWEP2024W034080205
• Study Type: observational
• Target: 80
• Locations: 1 country
• Sites: 1

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.

Conditions

Non-Small Cell Lung Cancer; Neoadjuvant Therapy; PD-1 Inhibitors; Immunotherapy

Keywords

Neoajuvant therapy; Ivonescimab; Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Pathological 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.

  At surgery (typically 3-6 months post-treatment initiation)

Secondary Outcomes (6)

• 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).

Study Arms (2)

Ivonescimab neoadjuvant therapy group

Patients in this group will receive ivonescimab as neoadjuvant therapy

Drug: Ivonescimab

PD-1 inhibitors neoadjuvant therapy group

Patients in this group will receive other PD-1 inhibitors as neoadjuvant therapy

Drug: PD-1 Inhibitors

Interventions

Ivonescimab DRUG

Patients in the experimental group will receive ivonescimab as neoadjuvant therapy.

Ivonescimab neoadjuvant therapy group

PD-1 Inhibitors DRUG

Patients in the positive control group will receive PD-1 inhibitors monotherapy as neoadjuvant treatment.

PD-1 inhibitors neoadjuvant therapy group

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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

You may qualify if:

• Patients with non-small cell lung cancer (Stage IB-IIIB) who require radical surgery following neoadjuvant therapy.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Peking University People's Hospital: lead

Study Sites (1)

Peking University People's Hospital

Beijing, Beijing Municipality, 100044, China

RECRUITING

Related Publications (5)

• Wang L, Luo Y, Ren S, Zhang Z, Xiong A, Su C, Zhou J, Yu X, Hu Y, Zhang X, Dong X, Meng S, Wu F, Hou X, Dai Y, Song W, Li B, Wang ZM, Xia Y, Zhou C. A Phase 1b Study of Ivonescimab, a Programmed Cell Death Protein-1 and Vascular Endothelial Growth Factor Bispecific Antibody, as First- or Second-Line Therapy for Advanced or Metastatic Immunotherapy-Naive NSCLC. J Thorac Oncol. 2024 Mar;19(3):465-475. doi: 10.1016/j.jtho.2023.10.014. Epub 2023 Oct 23.

  PMID: 37879536 RESULT

• Frentzas S, Austria Mislang AR, Lemech C, Nagrial A, Underhill C, Wang W, Wang ZM, Li B, Xia Y, Coward JIG. Phase 1a dose escalation study of ivonescimab (AK112/SMT112), an anti-PD-1/VEGF-A bispecific antibody, in patients with advanced solid tumors. J Immunother Cancer. 2024 Apr 19;12(4):e008037. doi: 10.1136/jitc-2023-008037.

  PMID: 38642937 RESULT

• Zhao S, Zhao H, Yang W, Zhang L. The next generation of immunotherapies for lung cancers. Nat Rev Clin Oncol. 2025 Aug;22(8):592-616. doi: 10.1038/s41571-025-01035-9. Epub 2025 Jun 17.

  PMID: 40528044 RESULT

• Chen Z, Yang F, Jiang Z, Sun L, Wu L, Han Z, Fan Y, Zhao Y, Li X, Xu H, Meng X, Liu Y, Zhang Z, Luo H, Ma X, Ma X, Shi Q, Zhang Z, Yang R, Wang P, Pan P, Ai X, Li J, Pu X, Wang Z, Fang J, He M, He Y, Guo S, Li J, Wang H, Zhang J, Chu Q, Liu X, Ying S, Wu H, Sun H, Ji Y, Zhou M, Cao C, Tang K, Li Z, Li D, Zhang Z, Li J, Zhou J, Yang H, Du Y, Yang H, Shi J, Chen H, Li W, Lu D, Hu M, Maxwell Wang Z, Li B, Xia M, Lu S. Ivonescimab plus chemotherapy versus tislelizumab plus chemotherapy as first-line treatment for advanced squamous non-small-cell lung cancer (HARMONi-6): a randomised, double-blind, phase 3 trial. Lancet. 2025 Nov 1;406(10515):2078-2088. doi: 10.1016/S0140-6736(25)01848-3. Epub 2025 Oct 19.

  PMID: 41125109 RESULT

• Xiong A, Wang L, Chen J, Wu L, Liu B, Yao J, Zhong H, Li J, Cheng Y, Sun Y, Ge H, Yao J, Shi Q, Zhou M, Chen B, Han Z, Wang J, Bu Q, Zhao Y, Chen J, Nie L, Li G, Li X, Yu X, Ji Y, Sun D, Ai X, Chu Q, Lin Y, Hao J, Huang D, Zhou C, Shan J, Yang H, Liu X, Wang J, Shang Y, Mei X, Yang J, Lu D, Hu M, Wang ZM, Li B, Xia M, Zhou C. Ivonescimab versus pembrolizumab for PD-L1-positive non-small cell lung cancer (HARMONi-2): a randomised, double-blind, phase 3 study in China. Lancet. 2025 Mar 8;405(10481):839-849. doi: 10.1016/S0140-6736(24)02722-3.

  PMID: 40057343 RESULT

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Immune Checkpoint Inhibitors

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses

Study Officials

• Fan Yang

  Peking University People's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hao Li

CONTACT

+86 13051713494; lihao_pkuhsc@163.com

Huiming Han

CONTACT

+86 18801398013; huimingpkuhsc@163.com

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Target Duration: 5 Years
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice President

Study Record Dates

• First Submitted: January 13, 2026
• First Posted: January 22, 2026
• Study Start: July 1, 2025
• Primary Completion (Estimated): December 21, 2026
• Study Completion (Estimated): October 30, 2027
• Last Updated: June 3, 2026

Record last verified: 2026-06

Locations

CN (1)