Clinical trial · Observational
Mechanism of Enhanced Efficacy of Ivonescimab in Neoadjuvant Therapy for Non-Small Cell Lung Cancer
Mechanisms of Enhanced Efficacy of Ivonescimab in Neoadjuvant Therapy for Non-Small Cell Lung Cancer
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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
Conditions (4)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Immunotherapy | — | UNRESOLVED | — |
| Neoadjuvant Therapy | — | UNRESOLVED | — |
| Non-Small Cell Lung Cancer | Lung Non-Small Cell Carcinoma | ALIAS | 0.90 |
| PD-1 Inhibitors | — | UNRESOLVED | — |
Interventions
Interventions (2)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Ivonescimab | Drug | — | UNRESOLVED |
| PD-1 Inhibitors | Drug | — | UNRESOLVED |
Design
Arms and outcomes
Arms (2)
- label
- Ivonescimab neoadjuvant therapy group
- description
- Patients in this group will receive ivonescimab as neoadjuvant therapy
- interventionNames
- Drug: Ivonescimab
- label
- PD-1 inhibitors neoadjuvant therapy group
- description
- Patients in this group will receive other PD-1 inhibitors as neoadjuvant therapy
- interventionNames
- Drug: PD-1 Inhibitors
Primary outcomes (1)
- measure
- Pathological Complete Response (pCR
- timeFrame
- At surgery (typically 3-6 months post-treatment initiation)
- description
- 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.
Eligibility
Eligibility (as posted)
- Sex
- All
Show eligibility criteria text
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.
References
Publications (5)
- RESULTWang 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
- RESULTFrentzas 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
- RESULTZhao 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
- RESULTChen 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
- RESULTXiong 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.