# Ivonescimab

Source: https://onco.cc/drugs/ivonescimab/  
OnCo record `ivonescimab` (Treatment). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

A Chinese bispecific that beat Keytruda head-to-head on progression-free survival in lung cancer, the first drug ever to do so.

## Summary

HARMONi-2 (China): PFS 11.1 vs 5.8 months versus pembrolizumab in PD-L1+ first-line NSCLC. Approved in China (2024) for EGFR-mutant NSCLC after TKI (HARMONi-A) and first-line PD-L1+ NSCLC. Summit Therapeutics holds Western rights; HARMONi (global, EGFR-mutant post-TKI) met PFS but OS was not statistically significant in 2025; HARMONi-3 (squamous and non-squamous first-line) ongoing. Spawned a wave of PD-(L)1×VEGF bispecifics (Pfizer/3SBio, BMS/BioNTech, Merck/LaNova).

## Fields

- Kind: Treatment
- Status: approved
- Last checked: 2026-09-04
- Code: AK112, SMT112
- Modality: Bispecific antibody (PD-1×VEGF)
- Mechanism: Tetravalent PD-1×VEGF-A bispecific with cooperative binding: VEGF binding increases PD-1 affinity, concentrating activity in tumour.
- Approvals: China 2024: EGFR-mutant NSCLC after TKI (with chemotherapy); first-line PD-L1+ NSCLC
- Dosing: IV infusion; 20 mg/kg every 3 weeks (China label; HARMONi-2)

## Sources

- ClinicalTrials.gov: trials of Ivonescimab: https://clinicaltrials.gov/search?intr=AK112

## Connected records

- cancers: [Advanced hepatocellular carcinoma (BCLC C)](https://onco.cc/cancers/hcc-advanced/), [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Gallbladder cancer](https://onco.cc/cancers/gallbladder/), [Hepatocellular carcinoma](https://onco.cc/cancers/hcc/), [Lung cancer (all types)](https://onco.cc/cancers/lung-cancer/), [Metastatic triple-negative breast cancer](https://onco.cc/cancers/tnbc-metastatic/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [PD-L1-high non-small-cell lung cancer without a driver mutation](https://onco.cc/cancers/pdl1-high-nsclc/), [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/)
- technologies: [Bispecific antibodies](https://onco.cc/technologies/bispecific-antibody/), [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/)
- targets: [PD-1](https://onco.cc/targets/pd1/), [VEGF / VEGFR](https://onco.cc/targets/vegf/)
- companies: [Akeso](https://onco.cc/companies/akeso/), [Summit Therapeutics](https://onco.cc/companies/summit-therapeutics/)
- trials: [A Multicenter, Single-arm Phase II Study to Evaluate the Efficacy and Safety of Fulzerasib (IBI351) in Combination With Ivonescimab (AK-112) in First-line Treatment of Advanced or Metastatic Non-small Cell Lung Cancer Patients With KRAS G12C Mutation](https://onco.cc/trials/nct06936644/), [A Phase Ib/II Clinical Study on AK112 Combined or Not Combined With AK119 in pMMR/MSS Colorectal Cancer](https://onco.cc/trials/nct05846867/), [A Phase II Clinical Study of AK104/AK112 in Combination With TT-00420 Tablet for Advanced HCC.](https://onco.cc/trials/nct07052253/), [A Phase II Study of AK146D1 in Combination With AK112 in Advanced Non-Small Cell Lung Cancer](https://onco.cc/trials/nct07669779/), [A Phase III Study of Ivonescimab + Chemo With/Without AK117 in Metastatic Pancreatic Cancer](https://onco.cc/trials/nct06953999/), [A Study of AK112 as Consolidation Treatment for Patients With Limited Stage Small-cell Lung Cancer Who Have Not Progressed Following Concurrent Chemor](https://onco.cc/trials/nct07010263/), [A Study of AK112 in Combination With VG2025 in Colorectal Cancer With Liver Metastases](https://onco.cc/trials/nct07357220/), [A Study of AK112 in Patients With Advanced Hepatocellular Carcinoma (HCC)](https://onco.cc/trials/nct06530251/), [A Study of AK112 With or Without AK117 in Metastatic Colorectal Cancer](https://onco.cc/trials/nct05382442/), [A Study of AK138D1 Alone or in Combination With Ivonescimab in Advanced Non-Small Cell Lung Cancer](https://onco.cc/trials/nct07623356/), [A Study of Chidamide Combined With Ivonescimab in the Treatment of Advanced Non-Small Cell Lung Cancer (NSCLC) With Acquired Resistance to Immunotherapy and Hig](https://onco.cc/trials/nct07412262/), [A Study of Ivonescimab in Combination With Dato-DXd or Osimertinib in People With Non-Small Cell Lung Cancer](https://onco.cc/trials/nct07535437/), [A Study of Ivonescimab in Combination With Enfortumab Vedotin vs Pembrolizumab in Combination With Enfortumab Vedotin in Metastatic Urothelial Carcinoma](https://onco.cc/trials/nct07815665/), [A Study of Ivonescimab in First-Line ES-SCLC](https://onco.cc/trials/nct07245446/), [A Study of Ivonescimab, Chemotherapy, and Stereotactic Radiosurgery for People With Non-Small Cell Lung Cancer](https://onco.cc/trials/nct07535463/), [A Study of Risvutatug Rezetecan in Combination With Ivonescimab in Participants With Advanced Solid Tumors (EMBOLD PanTumour-103)](https://onco.cc/trials/nct07602855/), [A Study of YL201 and Ivonescimab (AK112) in Advanced Solid Tumors](https://onco.cc/trials/nct07208773/), [A Study on Ivonescimab Plus Chemotherapy as Neoadjuvant Therapy for Borderline Resectable Pancreatic Cancer](https://onco.cc/trials/nct06944106/), [Adapted Guided Stereotactic Body Radiotherapy Combined With Chemotherapy and Enhancement of Novel Drug Ivonescimab for Pancreatic Cancer (ASCEND)](https://onco.cc/trials/nct06844422/), [AK112 and AK104 With or Without Chemotherapy in Advanced Non-small Cell Lung Cancer](https://onco.cc/trials/nct05904379/), [AK112 and Cadonilimab Combined With Chemotherapy for 1L Treatment of Metastatic Pancreatic Cancer](https://onco.cc/trials/nct06646055/), [AK112 Combined With GAP Conversion Therapy for Locally Advanced Gallbladder Cancer](https://onco.cc/trials/nct07767994/), [AK112 in Combination With Chemotherapy in Advanced Squamous Non-Small Cell Lung Cancer](https://onco.cc/trials/nct05840016/), [AK112 in Non-squamous Non-small Cell Lung Cancer (NSCLC)Patients With Actionable Genomic Alterations (AGA) Who Have Failed to Previous Tyrosine Kinase Inhibitor](https://onco.cc/trials/nct07158840/), [AK112 Neoadjuvant/Adjuvant Treatment for Resectable NSCLC](https://onco.cc/trials/nct05247684/), [AK112 or Placebo Plus Nab-Paclitaxel as First-line Treatment in Inoperable Locally Advanced/ Metastatic Triple-negative Breast Cancer](https://onco.cc/trials/nct06767527/), [AK112 Plus FOLFIRI Versus Bevacizumab Plus FOLFIRI as Second-line Treatment of MSS/pMMR Metastatic Colorectal Cancer](https://onco.cc/trials/nct07021950/), [AMT-116 in Combination With AK112 in Patients With Lung Cancer](https://onco.cc/trials/nct07590531/), [An Exploratory, Multi-cohort Phase II Study of Combination Therapy With AK104 and AK112 for Recurrent Ovarian Cancer](https://onco.cc/trials/nct06560112/), [Clinical Study of Ivonescimab for First-line Treatment of Metastatic NSCLC Patients With High PD-L1](https://onco.cc/trials/nct06767514/), [Combination Therapy of AK112 With Chemotherapy and/or Olaparib in Platinum-sensitive Ovarian Cancer](https://onco.cc/trials/nct06686030/), [ctDNA-MRD Guided Escalation of Ivonescimab and Docetaxel in Advanced NSCLC With Long-Term Responses to First-line Immunotherapy (CR1STAL-Adaptive)](https://onco.cc/trials/nct06951646/), [EA2197 ivonescimab: ivonescimab with gemcitabine and cisplatin versus standard chemo-immunotherapy in advanced biliary tract cancer](https://onco.cc/trials/ea2197-ivonescimab/), [First-in-Human Investigation of JMT108 Injection in Participants With Advanced Malignant Tumors](https://onco.cc/trials/nct06877650/), [HARMONi-2](https://onco.cc/trials/harmoni-2/), [HARMONi-3](https://onco.cc/trials/harmoni-3/), [HARMONi-A](https://onco.cc/trials/harmoni-a/), [Ivonescimab Alone And With Carboplatin/Pemetrexed For NSCLC](https://onco.cc/trials/nct07405190/), [Ivonescimab in Combination With Docetaxel in Advanced Non-Small Cell Lung Cancer](https://onco.cc/trials/nct06928389/), [Ivonescimab in Combination With Liposomal Irinotecan and 5-FU/LV in Potentially Resectable Biliary Tract Malignancies](https://onco.cc/trials/nct06993025/), [Ivonescimab Plus Chemotherapy in Patients With Initially Unresectable Colorectal Cancer Liver Metastases](https://onco.cc/trials/nct06848842/), [Ivonescimab With GnP and SBRT in Patients With Metastatic Pancreatic Cancer (WGOG-PAN 004)](https://onco.cc/trials/nct06991491/), [Ivonescimab(AK112/SMT112) in Combination With Stereotactic Body Radiation Therapy and Chemotherapy in Patients With Pancreatic Cancer](https://onco.cc/trials/nct06491472/), [Neoadjuvant Angiogenesis-Targeting Bispecific Chemoimmunotherapy for TNBC](https://onco.cc/trials/nct07743632/), [Neoadjuvant CAPOX Plus Ivonescimab Versus CAPOX for Locally Advanced Colon Cancer](https://onco.cc/trials/nct06790212/), [Neoadjuvant Short-Course Radiotherapy With or Without Chemotherapy and AK112 in Locally Advanced Rectal Cancer](https://onco.cc/trials/nct06718543/), [Neoadjuvant Therapy With Ivonescimab Combined With Chemotherapy for Triple-Negative Breast Cancer](https://onco.cc/trials/nct06977542/), [Paclitaxel Polymeric Micelles Plus Ivonescimab in Recurrent or Refractory SCLC](https://onco.cc/trials/nct07819591/), [Phase II Study of Anti-PD-1/VEGF Bispecific Antibody Ivonescimab in Patients With Previously Treated Metastatic Colorectal Cancer](https://onco.cc/trials/nct06959550/), [Phase II Study of Upfront SRT Plus Ivonescimab/Chemotherapy vs Ivonescimab/Chemotherapy in NSCLC Brain Mets](https://onco.cc/trials/nct07234877/), [Phase II Trial of Ivonescimab in Combination With Carboplatin + Docetaxel in Patients With Early-Stage Triple Negative Breast Cancer](https://onco.cc/trials/nct07017673/), [Phase III Study of AK112 for NSCLC Patients](https://onco.cc/trials/nct06396065/), [Prospective Multicenter Single-arm Trial: AK112 + Nab-paclitaxel/Carboplatin Neoadjuvant for TNBC](https://onco.cc/trials/nct07103447/), [SCRT Followed by AK112 in pMMR/MSS Mid-low Rectal Cancer](https://onco.cc/trials/nct07162714/), [SEVILLA](https://onco.cc/trials/sevilla/), [Short-course Radiotherapy Followed by AK112 and CAPOX as Neoadjuvant Therapy for Locally Advanced Rectal Cancer](https://onco.cc/trials/nct06802666/), [Study of RAS(ON) Inhibitors in Combination With Ivonescimab in Patients With Solid Tumors](https://onco.cc/trials/nct07397338/), [Testing Ivonescimab in Combination With Chemotherapy in Patients With Metastatic Colorectal Cancers Without Liver Metastases](https://onco.cc/trials/nct07359456/)
- pathways: [Cold tumours: immune deserts and exclusion](https://onco.cc/pathways/immune-desert-exclusion/), [PD-1 / PD-L1 immune checkpoint & T-cell activation](https://onco.cc/pathways/pd1-checkpoint/), [The angiogenic switch & tumour vessels](https://onco.cc/pathways/angiogenic-switch/), [The cancer-immunity cycle](https://onco.cc/pathways/cancer-immunity-cycle/), [VEGF angiogenesis](https://onco.cc/pathways/vegf-angiogenesis/)
- pairings: [PD-1 blockade + VEGF inhibition](https://onco.cc/pairings/io-plus-vegf/)
- roadmaps: [Immunotherapy roadmap: Coley's toxins → checkpoint inhibitors → engineered immunity](https://onco.cc/roadmaps/immunotherapy-roadmap/)
- people: [Caicun Zhou](https://onco.cc/people/zhou-caicun/), [Michelle Xia (Xia Yu)](https://onco.cc/people/xia-michelle/), [Qing Zhou](https://onco.cc/people/qing-zhou/), [Wenfeng Fang](https://onco.cc/people/fang-wenfeng/)
- key papers: [HARMONi-2: ivonescimab, a PD-1 x VEGF bispecific, beats pembrolizumab head-to-head in PD-L1-positive lung cancer](https://onco.cc/key-papers/paper-harmoni-2-lancet-2025/)
- terms: [Angiogenesis](https://onco.cc/terms/angiogenesis/)
- institutions: [Chinese Society of Clinical Oncology](https://onco.cc/institutions/csco/), [National Medical Products Administration / Center for Drug Evaluation](https://onco.cc/institutions/nmpa-cde/), [Shanghai Chest Hospital](https://onco.cc/institutions/shanghai-chest-hospital/)

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