On September 15, 2026 Akeso, Inc. (9926.HK) reported the presentation of positive overall survival (OS) results from the randomized, double-blind, multicenter, registrational Phase III HARMONi-2 study (AK112-303) at the 2026 World Conference on Lung Cancer (WCLC), organized by the International Association for the Study of Lung Cancer (IASLC). The study evaluated the company’s first-in-class next-generation immuno-oncology therapy, ivonescimab, versus pembrolizumab as first-line treatment for patients with PD-L1-positive (PD-L1 TPS ≥1%) locally advanced or metastatic non-small cell lung cancer (NSCLC).
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Professor Caicun Zhou, Principal Investigator of HARMONi-2, IASLC President, and Director of the Department of Oncology at Shanghai East Hospital, delivered an oral presentation in the session titled "The Breakthrough Immunotherapy for Advanced NSCLC," where he shared the complete results of the study.
As of the data cutoff on August 20, 2026, the median follow-up was 36 months, and a total of 234 overall survival (OS) events had occurred. For this OS analysis, a prespecified O’Brien-Fleming spending function was used, with a one-sided alpha of 0.0141.
Results showed that, compared with pembrolizumab, first-line treatment with ivonescimab significantly prolonged OS in patients with PD-L1-positive advanced NSCLC. This finding met the prespecified statistical significance threshold and demonstrated clear clinical benefit. The overall survival benefit was generally consistent across prespecified subgroups, with particularly pronounced benefit observed in the PD-L1-high population.
1. Intention-to-Treat (ITT) Population: Median OS of 30.8 Months with Ivonescimab, 27% Reduction in Risk of Death, with a Significant and Widening Long-Term Survival Advantage
In the ITT population, ivonescimab monotherapy significantly prolonged OS versus pembrolizumab, with median OS of 30.8 months versus 22.6 months (HR=0.73; 95% CI: 0.57–0.95; P=0.009), corresponding to a 27% reduction in the risk of death.
Ivonescimab demonstrated a clear long-term survival advantage over pembrolizumab, which further widened with longer follow-up: 2-year OS rates were 57.9% versus 48.0%, and 3-year OS rates were 45.0% versus 33.1%.
After treatment discontinuation, 46.0% of patients in the pembrolizumab arm received subsequent systemic therapy, compared with 36.4% in the ivonescimab arm.
2. Overcoming Traditional Anti-VEGF Treatment Restrictions: No Significant Increase in Bleeding Risk Observed in High-Risk Squamous Patients
Squamous NSCLC patients accounted for 45.5% of the HARMONi-2 population, and non-squamous patients for 54.5%. Among squamous patients treated with ivonescimab, 72.2% had central tumors, 10.0% had tumor cavitation or necrosis, and 6.7% had tumors encasing major vessels.
These populations are traditionally considered contraindicated or high-risk for anti-VEGF therapies and have long lacked effective treatment options. However, no apparent increase in bleeding risk was observed with ivonescimab, and these patients showed favorable benefit.
3. Significant OS Benefit Across PD-L1 Expression Levels, with Outstanding Benefit in the TPS ≥50% Subgroup
In the PD-L1 TPS ≥50% subgroup, median OS was not reached (NR) with ivonescimab versus 23.2 months with pembrolizumab (HR=0.58; 95% CI: 0.38–0.89).
In the PD-L1 TPS 1–49% subgroup, median OS was 28.5 months with ivonescimab versus 22.1 months with pembrolizumab (HR=0.85; 95% CI: 0.61–1.18).
4. Consistent OS Benefit by Histology, with Greater Advantage in Squamous Cell Carcinoma
In the squamous cell carcinoma subgroup, median OS was 30.5 months with ivonescimab versus 19.3 months with pembrolizumab (HR=0.65; 95% CI: 0.45–0.95).
In the non-squamous subgroup, median OS was 33.6 months with ivonescimab versus 25.6 months with pembrolizumab (HR=0.79; 95% CI: 0.55–1.14).
5. Favorable Overall Safety Profile with No New Safety Signals; Safety Characteristics Generally Consistent Between Arms
In May 2024, a prespecified interim analysis of progression-free survival (PFS) assessed by the Independent Data Monitoring Committee (IDMC) confirmed that HARMONi-2 met its primary PFS endpoint with statistically significant and clinically meaningful results. Median PFS was 11.14 months with ivonescimab versus 5.82 months with pembrolizumab (HR=0.51, P<0.0001). This indication was approved in China in 2025.
HARMONi-2 is the first randomized, double-blind, controlled Phase III clinical study globally to demonstrate statistically significant positive OS and PFS results versus pembrolizumab.
An international multicenter Phase III clinical study evaluating ivonescimab monotherapy versus pembrolizumab as first-line treatment for PD-L1-high NSCLC (HARMONi-7/AK112-3007) is currently progressing efficiently.
To date, ivonescimab has consistently achieved dual-positive OS and PFS results across multiple Phase III head-to-head trials against PD-1/L1 therapies and continues to expand into major solid tumors beyond lung cancer. The synergistic antitumor effects of ivonescimab’s dual "immuno-oncology + anti-angiogenesis" mechanism continue to be validated in both clinical research and real-world settings. Ivonescimab has the potential to provide a more effective treatment option with a manageable safety profile for cancer patients worldwide and to drive continued progress in oncology care.
(Press release, Akeso Biopharma, SEP 15, 2026, View Source [SID1234670837])