Background
Phase 3, double-blind RCT (50 hospitals, China); N=532; previously untreated unresectable stage IIIB–IV squamous NSCLC; ECOG 0–1. Prespecified interim overall-survival analysis. Ivonescimab is a PD-1/VEGF bispecific antibody; the comparator is the PD-1 inhibitor tislelizumab.
Results
Interventions and follow up: Arm A: Ivonescimab IV + paclitaxel/carboplatin ×4 cycles, then ivonescimab maintenance (n=266)
Arm B: Tislelizumab IV + paclitaxel/carboplatin ×4 cycles, then tislelizumab maintenance (n=266)
Primary endpoint: PFS by independent radiographic review (reported previously)
Key secondary endpoint: OS (this prespecified interim analysis)
mFollow up: 21.4 mo
Results: OS: 27.9 vs 23.7 mo; HR 0.66, 95% CI 0.50–0.87; P=.0017 (met prespecified boundary P<.0049)
Deaths: 84/266 (32%) vs 120/266 (45%)
OS by subgroup: benefit consistent across key subgroups
PFS (prior report): significantly prolonged with ivonescimab
Arm B: Tislelizumab IV + paclitaxel/carboplatin ×4 cycles, then tislelizumab maintenance (n=266)
Primary endpoint: PFS by independent radiographic review (reported previously)
Key secondary endpoint: OS (this prespecified interim analysis)
mFollow up: 21.4 mo
Results: OS: 27.9 vs 23.7 mo; HR 0.66, 95% CI 0.50–0.87; P=.0017 (met prespecified boundary P<.0049)
Deaths: 84/266 (32%) vs 120/266 (45%)
OS by subgroup: benefit consistent across key subgroups
PFS (prior report): significantly prolonged with ivonescimab
Adverse events
Grade ≥3 treatment-related: 69% vs 59%
Grade ≥3 haemorrhage: 3% vs 1%
Grade ≥3 haemorrhage: 3% vs 1%
Conclusions
In first-line advanced squamous NSCLC, ivonescimab plus chemotherapy significantly improved overall survival versus tislelizumab plus chemotherapy (HR 0.66) — the first randomized evidence that a PD-1/VEGF bispecific can extend survival over an established PD-1 inhibitor. Grade ≥3 bleeding was numerically higher but low in absolute terms.
Key Limitations
Conducted entirely in China (93% male population); generalizability uncertain. Interim OS analysis triggered early (204 vs planned 225 events) to meet regulatory timelines. Active PD-1 comparator (tislelizumab + chemo) rather than a pembrolizumab-based or chemotherapy-only control.
Clinical Context
Positions ivonescimab as a potential new first-line option in squamous NSCLC, where chemo-immunotherapy is standard. Approved in China; investigational in the US (Summit territories), where a BLA has been accepted with a PDUFA target of Nov 14, 2026. Not yet FDA-approved as of June 2026. Presented at the 2026 ASCO Annual Meeting plenary and published simultaneously in The Lancet.