Updated HARMONi Data at WCLC 2026 Show Durable Overall Survival Benefit for Ivonescimab in EGFR-Mutated NSCLC
核心洞察
Updated Phase III HARMONi results presented at WCLC 2026 show ivonescimab plus chemotherapy achieved an overall survival hazard ratio of 0.76 in EGFR (搜索)-mutated NSCLC.
With median follow-up extended to 23.2 months, western patients replicated the survival improvement previously seen in Asian patients, supporting regional consistency.
The Akeso-sponsored HARMONi-2 study reported ivonescimab monotherapy beat pembrolizumab on overall survival with a hazard ratio of 0.73 in PD-L1-positive NSCLC.
Summit Therapeutics reported updated overall survival (OS) results from the global Phase III HARMONi trial of ivonescimab plus chemotherapy in EGFR (搜索)-mutated non-small cell lung cancer (搜索) (NSCLC), presented September 15, 2026 at the International Association for the Study of Lung Cancer (IASLC) 2026 World Conference on Lung Cancer (WCLC 2026) in Seoul, Republic of Korea. The updated analysis, with a data cut-off in June 2026, showed an OS hazard ratio of 0.76 (95% CI: 0.61–0.95; nominal p=0.0151) in the global intention-to-treat (ITT) population, compared with placebo plus chemotherapy.
The HARMONi trial enrolled patients with epidermal growth factor receptor (EGFR (搜索))-mutated, locally advanced or metastatic non-squamous NSCLC who had progressed after treatment with a third-generation EGFR tyrosine kinase inhibitor (TKI), such as osimertinib. The study carries co-primary endpoints of progression-free survival (PFS) and OS; a statistically significant PFS benefit was demonstrated in the primary analysis.
Western Patients Converge With Asian Subgroup
At the April 2025 primary OS analysis, ivonescimab plus chemotherapy showed a positive trend that did not reach statistical significance, with a hazard ratio of 0.79 (95% CI: 0.62–1.01; p=0.057). Median OS was 16.8 months versus 14.0 months for placebo plus chemotherapy. At that time, median follow-up for western patients was only 9.2 months, shorter than the median OS.
In the June 2026 update, most western patients had discontinued or completed two years of treatment, with median follow-up of 23.2 months for western patients and 32.7 months for Asian patients (locked at the April 2025 analysis). The western subgroup demonstrated an OS hazard ratio of 0.76 (95% CI: 0.52–1.10), consistent with both the ITT population and the Asian subgroup.
"Updated results from the global Phase III HARMONi study show that ivonescimab combined with chemotherapy continued to demonstrate a consistent overall survival improvement compared with placebo plus chemotherapy in patients with EGFR (搜索)-mutated non-small cell lung cancer (搜索) following prior treatment with a third-generation EGFR TKI," said Antonio Passaro, M.D., Ph.D., Director of the Division of Thoracic Oncology at the European Institute of Oncology in Milan, Italy, and presenting author. "Importantly, with longer follow-up, the survival improvement observed in western patients was consistent with the global population, reinforcing the relevance of these results across geographic regions in a setting where patients continue to need additional treatment options after progression on EGFR-targeted therapy."
No additional safety signals were noted in the latest HARMONi data cut; the safety profile remained consistent with previous Phase III data of ivonescimab plus chemotherapy.
HARMONi-2: Monotherapy Versus Pembrolizumab
Also presented at WCLC 2026 were full detailed results from the protocol-specified interim OS analysis of HARMONi-2 (AK112-303), a single-region, multi-center Phase III study conducted in China and sponsored by Akeso, with all data generated, managed, and analyzed by Akeso. In this analysis, a secondary endpoint, ivonescimab monotherapy demonstrated a statistically significant and clinically meaningful OS improvement versus pembrolizumab monotherapy in patients with locally advanced or metastatic NSCLC with positive PD-L1 expression, achieving a hazard ratio of 0.73 (95% CI: 0.57–0.95; p=0.009).
Subgroup analyses, described as descriptive and not formally powered, showed an OS hazard ratio of 0.58 (95% CI: 0.38–0.89) in patients with PD-L1 score ≥50% (n=168; median OS not reached versus 23.2 months) and 0.85 (95% CI: 0.61–1.18) in those with PD-L1 score 1–49% (n=230; median OS 28.5 versus 22.1 months). By histology, the hazard ratio was 0.65 (95% CI: 0.45–0.95) in squamous disease (n=181; median OS 30.5 versus 19.3 months) and 0.79 (95% CI: 0.55–1.14) in non-squamous disease (n=217; median OS 33.6 versus 25.6 months).
Safety in HARMONi-2 remained acceptable and manageable, consistent with previous Phase III studies of ivonescimab, with no additional signals at longer treatment duration (median 14 cycles of ivonescimab versus 10 cycles of pembrolizumab). Over a median follow-up of 36.0 months, serious treatment-related adverse events (TRAEs) occurred in 59 patients (29.9%) on ivonescimab (n=198) versus 43 (21.6%) on pembrolizumab (n=200); TRAEs leading to discontinuation occurred in 8 (4.1%) versus 10 (5.0%), and TRAEs leading to death in 1 (0.5%) versus 3 (1.5%).
Regulatory Path and Broader Development
Summit's Biologics License Application (BLA) with the U.S. Food and Drug Administration (搜索) is based on HARMONi results and has a Prescription Drug User Fee Act (PDUFA) goal action date of November 14, 2026. The FDA accepted the BLA for filing in January 2026.
"The updated HARMONi overall survival analysis presented at WCLC 2026 provides important additional evidence of the consistency of ivonescimab's clinical profile across patient populations, with western patients showing consistent survival improvement to what was observed in Asian patients," said Dr. Maky Zanganeh, President and Co-Chief Executive Officer of Summit. "Together with the continued acceptable and manageable safety profile, these data reinforce our confidence in the HARMONi results as we work toward the potential approval of ivonescimab in the U.S."
Ivonescimab, known as SMT112 in Summit's license territories (North America, South America, Europe, the Middle East, Africa, and Japan) and as AK112 outside them, is a potential first-in-class investigational bispecific antibody combining PD-1 (搜索) blockade with anti-angiogenesis via VEGF (搜索) blockade in a single molecule. According to the companies, the molecule displays cooperative binding with multifold higher affinity to PD-1 in the presence of VEGF, and its tetravalent structure (four binding sites) is intended to enable higher avidity in the tumor microenvironment. Half-life is reported at 6 to 7 days after the first dose, increasing to approximately 10 days at steady-state dosing.
Ivonescimab was engineered by Akeso Inc. and is being studied in multiple Phase III trials. More than 4,000 patients have been treated in clinical studies globally, and more than 70,000 in a commercial setting in China, according to Akeso. Sixteen Phase III studies of ivonescimab are announced, ongoing, or completed, including five Summit-sponsored global studies. Five Phase III ivonescimab trials have read out to date, all with positive data — four in NSCLC and one in biliary tract cancer (搜索). Summit's development program has expanded into colorectal cancer (搜索) (HARMONi-GI3), urothelial carcinoma (搜索) (HARMONi-GU1, a Phase II/III study combining ivonescimab with the antibody-drug conjugate enfortumab vedotin), and first-line NSCLC (HARMONi-3 and HARMONi-7). Ivonescimab is not approved by any regulatory authority in Summit's license territories; it was initially approved for marketing authorization in China in May 2024.