Evidence map›Paper›PMID 40057343›Full record

Trial reportLancet (London, England)2025

Ivonescimab versus pembrolizumab for PD-L1-positive non-small cell lung cancer (HARMONi-2): a randomised, double-blind, phase 3 study in China.

Anwen Xiong, Lei Wang, Jianhua Chen, Lin Wu, Baogang Liu, Jun Yao, Hua Zhong, Jie Li, Ying Cheng, Yulan Sun and 35 more

Erratum issued 3 registry-linked trialsAbstract readRandomized Controlled TrialClinical Trial, Phase IIIMulticenter Study
PubMed Publisher
In one paragraph

Trial report in Lancet (London, England), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to 3 registered trials, which are not on this map. Cited by 109 papers, 11 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
109citing papers in PubMed, 11 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT05499390 phase3active not recruitingnot on this map

A Randomized Controlled, Multi-center Phase III Clinical Trial of AK112 Versus Pembrolizumab as First-line Treatment for PD-L1-Positive Locally-Advanced or Metastatic Non-Small Cell Lung Cancer

TypeinterventionalSponsorAkesoRan2022 to 2026Enrolled398ConditionsAdvanced Non-small-cell Lung CancerArmsAK112, Pembrolizumab
NCT07009925 phase2not yet recruitingnot on this map

Ivonescimab Combined With Polymeric Micelles Paclitaxel(Pm-Pac) and Platinum (Cisplatin/Carboplatin) as First-line Treatment for Patients With Advanced Squamous NSCLC: A Multicenter, Open-label, Single-arm Clinical Study.

TypeinterventionalSponsorJiangsu Cancer Institute & HospitalRan2025 to 2028Enrolled38ConditionsSquamous Cell Lung CancerArmsIvonescimab 20mg/kg intravenous every 3 weeks
NCT07359040 recruitingnot on this map

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

Typeobservational_patient_registrySponsorPeking University People's HospitalRan2025 to 2027Enrolled80ConditionsNon-Small Cell Lung Cancer, Neoadjuvant Therapy, PD-1 Inhibitors, ImmunotherapyArmsIvonescimab, PD-1 Inhibitors
3 · Its place in the literature

Who cites it

109 citing papers in PubMed, 11 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Pooled it
  7. Pooled it
  8. Pooled it
  9. Pooled it
  10. Progress in immunotherapy for resectable head and neck squamous cell carcinoma.Medical oncology (Northwood, London, England) · 2025
    Pooled it
  11. Pooled it
  12. Trial
  13. Trial
  14. Trial
  15. Trial
  16. Trial
  17. Review
  18. Review
  19. Review
  20. Review

49 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

45 authors.

Anwen XiongShanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
Lei WangShanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
Jianhua ChenHunan Cancer Hospital, Changsha, China.
Lin WuHunan Cancer Hospital, Changsha, China.
Baogang LiuHarbin Medical University Cancer Hospital, Harbin, China.
Jun YaoThe First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China.
Hua ZhongShanghai Chest Hospital, Shanghai, China.
Jie LiThe First Affiliated Hospital of Gannan Medical University, Ganzhou, China.
Ying ChengJilin Cancer Hospital, Changchun, China.
Yulan SunShandong Cancer Hospital and Institute, Jinan, China.
Hui GeThe Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
Jifang YaoThe Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
Qin ShiFuzhou Tuberculosis Prevention and Treatment Hospital, Fuzhou, China.
Ming ZhouAffiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China.
Bolin ChenHunan Cancer Hospital, Changsha, China.
Zhengxiang HanThe Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
Jinliang WangThe Fifth Medical Center of the Chinese People's Liberation Army General Hospital, Beijing, China.
Qing BuThe First Affiliated Hospital of Guangxi Medical University, Nanning, China.
Yanqiu ZhaoHenan Cancer Hospital, Zhengzhou, China.
Junqiang ChenFujian Cancer Hospital, Fuzhou, China.
Ligong NiePeking University First Hospital, Beijing, China.
Gaofeng LiYunnan Cancer Hospital, Kunming, China.
Xingya LiFirst Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Xinmin YuZhejiang Cancer Hospital, Hangzhou, China.
Yinghua JiThe First Affiliated Hospital of Xinxiang Medical University, Xinxiang, China.
Daqiang SunTianjin Chest Hospital, Tianjin, China.
Xiaohong AiThe First Affiliated Hospital of University of South China, Hengyang, China.
Qian ChuHuazhong University of Science and Technology Tongji Hospital, Tongji Medical College, Wuhan, China.
Yu LinFujian Cancer Hospital, Fuzhou, China.
Jiqing HaoThe First Affiliated Hospital of Anhui Medical University, Hefei, China.
Dingzhi HuangTianjin Medical University Cancer Institute and Hospital, Tianjin, China.
Chengzhi ZhouThe First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Jinlu ShanDaping Hospital, Army Medical University, Chongqing, China.
Hongzhong YangChangsha Central Hospital, Changsha, China.
Xuewen LiuThird Xiangya Hospital of Central South University, Changsha, China.
Jing WangThe Affiliated Hospital of Qingdao University, Qingdao, China.
Yanhong ShangAffiliated Hospital of Hebei University, Baoding, China.
Xiaodong MeiThe First Affiliated Hospital of USTC (Anhui Provincial Hospital), Hefei, China.
Jie YangAkeso Biopharma, Zhongshan, China.
Dongmei LuAkeso Biopharma, Zhongshan, China.
Mingxiu HuAkeso Biopharma, Zhongshan, China.
Zhongmin Maxwell WangAkeso Biopharma, Zhongshan, China.
Baiyong LiAkeso Biopharma, Zhongshan, China.
Michelle XiaAkeso Biopharma, Zhongshan, China.
Caicun ZhouShanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China; Shanghai East Hospital, Shanghai, China. Electronic address: caicunzhoudr@163.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundIvonescimab is a bispecific antibody against programmed cell death protein 1 and vascular endothelial growth factor, yielding promising clinical outcomes for patients with advanced non-small cell lung cancer in early-phase studies. We compared the efficacy and safety of ivonescimab with pembrolizumab in patients with programmed cell death ligand-1 (PD-L1)-positive advanced non-small cell lung cancer.

methodsHARMONi-2 is a randomised, double-blind, phase 3 trial across 55 hospitals in China. Eligible patients were aged 18 years or older and had locally advanced or metastatic PD-L1-positive non-small cell lung cancer without sensitising epidermal growth factor receptor mutations or anaplastic lymphoma kinase translocations and an Eastern Cooperative Oncology Group performance-status of 0 or 1. Patients were randomly assigned (1:1) to receive 20 mg/kg ivonescimab or 200 mg pembrolizumab intravenously every 3 weeks. Randomisation was stratified by histology, clinical stage, and PD-L1 expression. The primary endpoint was progression-free survival (PFS) assessed by a masked independent radiographic review committee per RECIST v1.1 in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT05499390; recruitment is complete, with the trial ongoing and final analysis to be reported later.

findingsBetween Nov 9, 2022, and Aug 26, 2023, 398 (45%) of 879 screened patients were randomly assigned to receive ivonescimab (n=198) or pembrolizumab (n=200). At the preplanned interim analysis, median PFS was significantly longer with ivonescimab than with pembrolizumab (11·1 vs 5·8 months; stratified hazard ratio [HR] 0·51 [95% CI 0·38-0·69]; one-sided p<0·0001). The PFS benefit of ivonescimab over pembrolizumab was broadly consistent within prespecified subgroups, including patients with PD-L1 tumour proportion score (TPS) 1-49% (HR 0·54 [95% CI 0·37-0·78]) and PD-L1 TPS of 50% of higher (HR 0·48 [0·29-0·79]). Grade 3 or higher treatment-related adverse events occurred in 58 (29%) patients with ivonescimab and 31 (16%) patients with pembrolizumab. Immune-related adverse events of grade 3 or higher were observed in 14 (7%) of 197 patients on ivonescimab and 16 (8%) of 199 patients on pembrolizumab. Ivonescimab demonstrated a manageable safety profile in patients with both squamous and non-squamous non-small cell lung cancer. In patients with squamous cell carcinoma, grade 3 or higher treatment-related adverse events were comparable between the two groups.

interpretationIvonescimab significantly improved PFS compared with pembrolizumab in previously untreated patients with advanced PD-L1 positive non-small cell lung cancer. Therefore, ivonescimab might represent another treatment option in the first-line setting for PD-L1-positive advanced non-small cell lung cancer.

fundingAkeso Biopharma.

Indexed as

Antibodies, BispecificAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalB7-H1 AntigenCarcinoma, Non-Small-Cell LungLung NeoplasmsAdultAgedChinaDouble-Blind MethodFemaleHumansImmune Checkpoint InhibitorsMaleMiddle AgedProgression-Free SurvivalAntibodies, BispecificAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalB7-H1 AntigenCD274 protein, humanImmune Checkpoint Inhibitorspembrolizumab

Identifiers

PMID40057343

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.