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Ivonescimab

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

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).

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IgG antibody backbone (PDB 1IGT)
RCSB PDB

No public structure of ivonescimab; representative IgG shown.

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1.Tetravalent antibody binds VEGF-A in the tumour microenvironment

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.
Brand / code
AK112, SMT112
Dosing & schedule
Route
IV infusion
Schedule
20 mg/kg every 3 weeks (China label; HARMONi-2)
Dose modifications
Standard immune-mediated event algorithm plus VEGF-class precautions (bleeding, hypertension, proteinuria)
Monitoring
Blood pressure, urine protein, thyroid, LFTs

Source: www.akesobio.com. Doses are for orientation; the current label governs.

Regulatory

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  1. 24 May 2024ApprovalChina

    EGFR-mutant NSCLC after TKI, with chemotherapy (HARMONi-A) source

  2. Apr 2025ApprovalChina

    First-line PD-L1+ NSCLC (HARMONi-2) source

  3. Jan 2026Filing / dealUS

    BLA submitted by Summit for EGFR-mutant NSCLC after TKI (HARMONi) source

  4. 14 Nov 2026PDUFA dateUS

    PDUFA target date source

Approvals

RegionYearIndication
China2024EGFR-mutant NSCLC after TKI (with chemotherapy); first-line PD-L1+ NSCLC

Safety

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Toxicity profile
Adverse event
Proteinuria
Hypertension
Anaemia
AST increased
Hypothyroidism
Haemorrhage (low grade)

Events listed without rates were not read from a primary source; see the label. Blank cells mean the figure was not sourced, not that it is zero.

Cost & access

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Cost & access
CountryReimbursement
ChinaNMPA approved 2024; NRDL inclusion 2025
United StatesInvestigational; BLA under review (PDUFA 14 November 2026)

List prices are manufacturer or Medicare figures where publicly disclosed; net prices after rebates are usually lower. Reimbursement changes; check the payer.

Trials

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ClinicalTrials.gov · phase 2/3
refreshed 2026-09-09
114 studies57 recruiting94 Phase 28 Phase 3
Search “Ivonescimab” on ClinicalTrials.gov →
Counts are from a name search and may include unrelated studies; up to 100 studies are summarised.

Recruiting now (live from ClinicalTrials.gov)

Recruiting trials near you · live from ClinicalTrials.gov
Ivonescimab
intervention: Ivonescimab
Open on ClinicalTrials.gov →

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Key papers

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Latest papers

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Literature trend54 papers in the last 12 months+125% vs prior 12How this is computed
Latest papers · live from Europe PMC
Open in Europe PMC

Query for this drug: (TITLE:"Ivonescimab" OR ABSTRACT:"Ivonescimab" OR TITLE:"AK112" OR ABSTRACT:"AK112" OR TITLE:"SMT112" OR ABSTRACT:"SMT112") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Ivonescimab, not a curated reading list.

Connected

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