David R Spigel MD; ASCO 2026: Bispecific PD-1/VEGF Antibody Ivonescimab Extends Life in Patients with Untreated Advanced Non–Small Cell Lung Cancer: Phase 3 HARMONi-6 trial
CHICAGO, USA—The bispecific antibody ivonescimab (that targets the PD-1 and VEGF molecules) has extended overall survival in patients with untreated advanced squamous non-small cell lung cancer in the latest data from the HARMONi-6 trial reported at the 2026 Annual Meeting of the American Society of Clinical Oncology by Chen Zhiwei from Jiao Tong University in Shanghai, China. Peter Goodwin discusses the findings with ASCO expert David R Spigel MD, President & Chief Medical Officer at the Sarah Cannon Research Institute in Nashville, Tennessee, USA
Bispecific PD-1/VEGF Antibody Ivonescimab Extends Life in Patients with Untreated Advanced Non–Small Cell Lung Cancer: Phase 3 HARMONi-6 trial
An interview with:
David R Spigel MD, President & Chief Medical Officer, Sarah Cannon Research Institute, Nashville, Tennessee, USA commenting on research by:
Chen Zhiwei, Shanghai Chest Hospital, Shanghai, Jiao Tong University, School of Medicine, Shanghai, Shanghai, China
CHICAGO, USA—The bispecific antibody ivonescimab (that targets the PD-1 and VEGF molecules) has extended overall survival in patients with untreated advanced squamous non-small cell lung cancer in the latest data from the HARMONi-6 trial reported at the 2026 Annual Meeting of the American Society of Clinical Oncology by Chen Zhiwei from Jiao Tong University in Shanghai, China.
Peter Goodwin discusses the findings with ASCO expert David R Spigel MD, President & Chief Medical Officer at the Sarah Cannon Research Institute in Nashville, Tennessee, USA
IN: Peter Goodwin here at the American ….
OUT:for the Audio Journal of Oncology. 6:14secs
SOURCE:
JOURNAL OF CLINICAL ONCOLOGY:
https://ascopubs.org/doi/10.1200/JCO.2026.44.17_suppl.LBA4
Ivonescimab plus chemotherapy versus tislelizumab plus chemotherapy in previously untreated advanced squamous non–small cell lung cancer: Overall survival results of the phase 3 HARMONi-6 trial.
Authors:
Chen Zhiwei, Shun Lu et al
J Clin Oncol 44, LBA4(2026)
Volume 44, Number 17_suppl
DOI: 10.1200/JCO.2026.44.17_suppl.LBA4
ASCO 2026 Abstract LBA4
Background:
In the prespecified interim analysis of progression-free survival (PFS) from the HARMONi-6 study, ivonescimab combined with chemotherapy significantly improved PFS compared with tislelizumab plus chemotherapy in patients with previously untreated advanced squamous NSCLC(sq-NSCLC). Here we report the results of the prespecified overall survival (OS) analysis.
Methods:
Patients with previously untreated stage III-IV sq-NSCLC were randomly assigned (1:1) to receive ivonescimab 20 mg/kg every 3 weeks (Q3W) or tislelizumab 200 mg Q3W, each in combination with paclitaxel (175 mg/m²) and carboplatin (AUC 5) for 4 cycles, followed by maintenance ivonescimab or tislelizumab monotherapy. Randomization was stratified by disease stage (IIIB/IIIC versus IV) and PD-L1 tumor proportion score (TPS; ≥1% versus <1%). The primary endpoint was PFS assessed by independent radiographic review committee per RECIST v1.1. OS was a key secondary endpoint and was hierarchically tested using a closed sequential testing procedure. PFS was tested first at one-sided α level of 0.025, OS was tested at the same α only after statistical significance for PFS was established. This analysis represents the first planned OS analysis with an efficacy boundary of one-sided P=0.0049.
Results:
A total of 532 patients were randomly assigned (n=266 per arm). As of February 27, 2026, at a median follow-up of 21.4 months, ivonescimab plus chemotherapy significantly improved OS compared with tislelizumab plus chemotherapy. Median OS was 27.9 months (95% CI, 27.89 to NE) with ivonescimab plus chemotherapy versus 23.7 months (95% CI, 20.11 to NE) with tislelizumab plus chemotherapy (hazard ratio [HR], 0.66; 95% CI, 0.50 to 0.87; one-sided P =0.0017), meeting the prespecified boundary (P<0.0049) for statistical significance.The OS benefit was consistent across prespecified subgroups. Among patients with PD-L1 TPS <1%, median OS was NE versus 18.6 months (HR, 0.64; 95% CI, 0.43 to 0.96). Among patients with PD-L1 TPS≥1%, median OS was NE versus 27.3 months (HR, 0.68; 95% CI, 0.46 to 0.99). The safety profile of ivonescimab plus chemotherapy was manageable and consistent with prior reports, with no new safety signals observed.
Conclusion: Ivonescimab plus chemotherapy demonstrated a statistically significant and clinically meaningful improvement in OS compared with tislelizumab plus chemotherapy in previously untreated patients with advanced sq-NSCLC. Notably, ivonescimab plus chemotherapy is the first regimen to show clinical superiority over an active PD-1 inhibitor control arm in the first-line setting. The dual-targeted approach of ivonescimab delivers improved survival outcomes with a favorable risk-benefit profile, establishing a compelling new standard of care in the management of advanced sq-NSCLC. Clinical trial information: NCT05840016.
David Spigel MD on Chen Zhiwei ASCO 2026TEXT
October 16, 2026
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