Ivonescimab Improves Overall Survival in Phase 3 HARMONi-6 Trial for Squamous NSCLC

New Phase 3 data presented at the 2026 American Society of Clinical Oncology Annual Meeting suggest that ivonescimab, a PD-1/VEGF bispecific antibody, may redefine first-line treatment expectations for patients with advanced squamous non-small cell lung cancer (sq-NSCLC). Results from the HARMONi-6 study demonstrated statistically significant improvements in both overall survival (OS) and progression-free survival (PFS) when ivonescimab was combined with chemotherapy and compared against the PD-1 inhibitor tislelizumab plus chemotherapy.¹

The findings, simultaneously published in The Lancet, represent one of the first Phase 3 studies to demonstrate superiority over a PD-1 inhibitor plus chemotherapy regimen in a head-to-head trial among patients with advanced sq-NSCLC.¹,²

How did ivonescimab perform against standard PD-1-based therapy?

The randomized Phase 3 HARMONi-6 trial enrolled 532 patients with advanced sq-NSCLC. At a prespecified interim analysis with a median follow-up of 21.4 months, investigators reported a 34% reduction in the risk of death for patients receiving ivonescimab plus chemotherapy compared with those receiving tislelizumab plus chemotherapy (hazard ratio [HR] = 0.66; p=0.0017).¹,²

Median overall survival reached 27.9 months in the ivonescimab arm versus 23.7 months in the control arm. The survival advantage appeared to widen over time, with 24-month overall survival rates of 64.7% and 48.6%, respectively.¹,²

The study also met its progression-free survival endpoint. Previously reported results showed a median PFS of 11.1 months with ivonescimab plus chemotherapy compared with 6.9 months for the control regimen (HR = 0.60; p<0.0001).¹

According to the investigators, survival benefits were observed across multiple predefined patient subgroups, including patients with both PD-L1-positive and PD-L1-negative tumors, as well as those with high metastatic burden.¹

Why is the HARMONi-6 study important for lung cancer treatment?

Current first-line treatment for advanced NSCLC without actionable driver mutations commonly includes a PD-1 or PD-L1 inhibitor combined with platinum-based chemotherapy. Despite substantial improvements over chemotherapy alone, few therapies have demonstrated superiority against established immunotherapy-based regimens in Phase 3 studies.²

Professor Shun Lu, director of the Lung Cancer Center at Shanghai Chest Hospital and principal investigator of HARMONi-6, described the findings as a potential milestone for the field.

“HARMONi-6 is the first global Phase 3 study in lung cancer to show statistically significant improvements in both OS and PFS compared with PD-1 plus chemotherapy,” Lu said in a statement.¹

The trial also marks a notable moment for Chinese oncology drug development. According to Akeso, the HARMONi-6 results were selected for presentation during an ASCO Plenary Session, representing the first time a China-originated investigational oncology therapy has been featured in the meeting’s plenary program.¹

What do the safety findings show?

Safety findings were generally consistent with prior ivonescimab studies. Grade 3 or higher treatment-related adverse events occurred in 69.2% of patients receiving ivonescimab plus chemotherapy compared with 58.9% of patients receiving tislelizumab plus chemotherapy. Rates of treatment discontinuation and treatment-related deaths were reported as similar between treatment groups.¹

Ivonescimab is currently being evaluated across more than 30 clinical settings, including 15 Phase 3 trials spanning multiple tumor types. The positive HARMONi-6 results further strengthen interest in dual-targeting immunotherapy approaches designed to simultaneously inhibit immune checkpoint signaling and tumor angiogenesis.¹

For patients with advanced squamous NSCLC, the data suggest that combining PD-1 and VEGF inhibition within a single molecule may offer a new strategy for extending survival beyond what has been achieved with current immunotherapy standards.¹,²

References

1. HARMONi-6 demonstrates significant overall survival benefit (HR=0.66): ivonescimab plus chemotherapy superior to PD-1 plus chemotherapy in first-line sq-NSCLC landmark results to be presented at ASCO 2026 plenary session. (2026 May 31). Akeso. https://www.prnewswire.com/news-releases/harmoni-6-demonstrates-significant-overall-survival-benefit-hr0-66-ivonescimab-plus-chemotherapy-superior-to-pd-1-plus-chemotherapy-in-first-line-sq-nsclc-landmark-results-to-be-presented-at-asco-2026-plenary-session-302786433.html?utm_source=chatgpt.com
2. Ivonescimab with chemotherapy demonstrated a statistically significant overall survival benefit compared to tislelizumab plus chemotherapy in first-line treatment of patients with squamous NSCLC in the HARMONi-6 study conducted by Akeso in China. (2026 May 31). Summit Therapeutics. https://smmttx.com/news/press-releases/news-details/2026/Ivonescimab-with-Chemotherapy-Demonstrated-a-Statistically-Significant-Overall-Survival-Benefit-Compared-to-Tislelizumab-Plus-Chemotherapy-in-1L-Treatment-of-Patients-with-Squamous-NSCLC-in-the-HARMONi-6-Study-Conducted-by-Akeso-in-China/default.aspx