Ivonescimab Bests Pembrolizumab on Overall Survival in PD-L1+ NSCLC

According to a preplanned secondary end point analysis of the phase 3 HARMONi-2 trial (NCT05499390), ivonescimab (AK112) monotherapy demonstrated a statistically significant improvement in overall survival (OS) compared with pembrolizumab (Keytruda) monotherapy in patients with PD-L1–positive locally advanced or metastatic non–small cell lung cancer (NSCLC).¹

Detailed results from the interim OS analysis, including the magnitude of the treatment effect, are expected to be presented at an upcoming international medical conference and published in a peer-reviewed journal.

The latest findings build on the study's previously reported progression-free survival (PFS) results. In May 2024, a prespecified interim analysis found that ivonescimab met the primary end point of PFS, with a median PFS of 11.14 months compared with 5.82 months for pembrolizumab. In the primary analysis, the PFS hazard ratio was 0.51 (95% CI, 0.38-0.69; P <.0001) based on independent radiologic review.

“To date, ivonescimab has achieved dual positive OS and PFS outcomes across multiple [p]hase [3] head-to-head trials vs PD-1/PD-L1 therapies. This growing body of evidence strengthens our confidence in its potential across a broader range of solid tumors,” Dr Yu Xia, president and CEO of Akeso, stated in a news release.¹ “With its unique dual mechanism of action combining immunotherapy and anti-angiogenesis, we believe ivonescimab offers a more effective treatment option for patients and will contribute meaningfully to the evolving oncology treatment landscape."

Safety Profile

The safety profile of ivonescimab was reported as manageable in a previously published analysis of HARMONi-2, although grade 3 or higher treatment-related adverse events (TRAEs) occurred more frequently with ivonescimab than with pembrolizumab, at 29% and 16%, respectively.³ In the analysis, grade 3 or higher immune-related adverse events occurred in 7% of patients in the ivonescimab group and 8% in the pembrolizumab group.

About the HARMONi-2 Trial

HARMONi-2 is a randomized, double-blind, multicenter, registrational phase 3 study in China evaluating ivonescimab monotherapy against pembrolizumab monotherapy as first-line treatment for patients with locally advanced or metastatic NSCLC whose tumors express PD-L1 at a tumor proportion score (TPS) of at least 1%.²

HARMONi-2 is part of a broader clinical development program for ivonescimab in NSCLC. The phase 3 HARMONi trial (NCT06396065) is evaluating ivonescimab plus chemotherapy compared with placebo plus chemotherapy in patients with EGFR-mutated, locally advanced or metastatic nonsquamous NSCLC following treatment with a third-generation EGFR tyrosine kinase inhibitor. Another phase 3 study, HARMONi-3 (NCT05899608), is evaluating ivonescimab plus chemotherapy against pembrolizumab plus chemotherapy in the first-line treatment of metastatic squamous or nonsquamous NSCLC regardless of PD-L1 expression.

About Ivonescimab and Clinical Development

Ivonescimab is a bispecific antibody designed to simultaneously target PD-1 and vascular endothelial growth factor (VEGF). Its tetravalent structure is intended to combine the immune-mediated effects associated with PD-1 blockade with the antiangiogenic effects associated with VEGF inhibition in a single molecule. The molecule has been designed with cooperative binding properties, with higher affinity for PD-1 in the presence of VEGF.

While ivonescimab is approved and commercially available in China, the agent remains investigational in the United States and Europe, with a biologics license application for use in pretreated EGFR-mutated NSCLC currently under FDA review based on the HARMONi trial.

REFERENCES

1. Ivonescimab Meets Overall Survival Key Secondary Endpoint in Interim Analysis of Phase III HARMONi-2 Study, Demonstrating Statistically Significant and Clinically Meaningful Benefit Versus Pembrolizumab in First-Line PD-L1-Positive NSCLC. News release. Akeso. September 2, 2026. Accessed September 3, 2026. https://www.prnewswire.com/news-releases/ivonescimab-meets-overall-survival-key-secondary-endpoint-in-interim-analysis-of-phase-iii-harmoni-2-study-demonstrating-statistically-significant-and-clinically-meaningful-benefit-versus-pembrolizumab-in-first-line-pd-l1-positiv-302867930.html

2. AK112 in Advanced Non-Small Cell Lung Cancer. ClinicalTrials.gov. Updated March 9, 2026. Accessed September 3, 2026. https://clinicaltrials.gov/study/NCT05499390

3. Xiong A, Wang L, Chen J, et al. Ivonescimab versus pembrolizumab for PD-L1-positive non-small cell lung cancer (HARMONi-2): a randomised, double-blind, phase 3 study in China. Lancet. 2025;405(10481):839-849. doi:10.1016/S0140-6736(24)02722-3