The statistically significant positive OS results of ivonescimab versus pembrolizumab in the first-line treatment of PD-L1-positive NSCLC (HARMONi-2 study) were announced at WCLC 2026
At the 2026 World Conference on Lung Cancer (WCLC), held by the International Association for the Study of Lung Cancer (IASLC) on September 13–15, 2026, statistically significant positive overall survival (OS) results were announced from HARMONi-2/AK112-303. This randomized, double-blind, controlled, multicenter, registration Phase III trial compared Akeso’s (9926.HK) ivonescimab (trade name: Yidafang®), the world’s first cornerstone drug of immuno-oncology 2.0, with pembrolizumab as first-line treatment for patients with PD-L1-positive (TPS ≥1%) locally advanced or metastatic non-small cell lung cancer (NSCLC). The findings were selected for an oral Late-Breaking Abstract (LBA) presentation and the official WCLC press program.
On September 13, the WCLC official website released the Abstract data of HARMONi-2 research OS. On September 15, Professor Zhou Caicun, the principal investigator of HARMONi-2, chairman of IASLC, and director of the Oncology Department of Shanghai Oriental Hospital, will give a formal oral report (Oral) at the conference to share the complete results of HARMONi-2 research with the global industry.
As of August 20, 2026, the median follow-up time was 36 months, and a total of 234 overall survival (OS) events had occurred. The study followed the preset O’Brien-Fleming consumption function, and the one-sided α value of this OS analysis was 0.0141.
The results of the study show that compared with pembrolizumab, ivonescimab in the first-line treatment of PD-L1-positive advanced NSCLC significantly prolongs the overall survival (OS) of patients, reaching preset statistical significance and having clear clinical benefit; preset subgroup analysis generally showed a consistent OS benefit trend, especially among those with high PD-L1 expression.
ITT population: The median OS in the ivonescimab group reached 30.8 months, and the risk of death decreased by 27%.
In the ITT population, ivonescimab single agent significantly prolonged OS compared with pembrolizumab. The median OS of the two groups was 30.8 months vs. 22.6 months, HR=0.73 (95% CI: 0.57–0.95), and the risk of death was reduced by 27%, P=0.009.
Breaking through the traditional taboos of anti-VEGF treatment, no significant increase in bleeding risk was seen in high-risk squamous cell carcinoma patients
The proportion of squamous NSCLC patients enrolled in the HARMONi-2 study was 45.5%, and the proportion of non-squamous cell carcinoma patients was 54.5%. Among patients with squamous cell carcinoma treated with ivonescimab, 72.2% were central type, 10.0% had tumor cavitation or necrosis, and 6.7% had tumors surrounding important blood vessels;
These groups are considered contraindicated or high-risk in traditional anti-VEGF treatment and have long lacked effective treatment options. However, ivonescimab treatment has not shown a significant increase in bleeding risk and has shown good benefits.
Regardless of PD-L1 expression level, ivonescimab brings consistent OS benefit, especially for people with TPS ≥50%.
In the PD-L1 TPS ≥50% subgroup, the OS HR of the ivonescimab group compared with the pembrolizumab group was 0.58 (95% CI: 0.38–0.89), and the risk of death was reduced by 42%.
In the PD-L1 TPS 1–49% subgroup, the OS HR of the ivonescimab group compared with the pembrolizumab group was 0.85 (95% CI: 0.61–1.18), with a relative reduction of 15% in the risk of death.
Regardless of squamous cell carcinoma or non-squamous cell carcinoma, ivonescimab brings consistent OS benefit
In the squamous cell carcinoma subgroup, the OS HR of the ivonescimab group compared with the pembrolizumab group was 0.65 (95% CI: 0.45–0.95), and the risk of death was reduced by 35%.
In the non-squamous cell carcinoma subgroup, the OS HR of the ivonescimab group compared with the pembrolizumab group was 0.79 (95% CI: 0.55–1.14), and the risk of death was reduced by 21%.
The overall safety of ivonescimab is excellent, and no new safety signals were observed; the safety characteristics of the two groups are generally consistent
In May 2024, the interim analysis of the preset progression-free survival (PFS) of the HARMONi-2 study evaluated by IDMC showed that the study reached the primary endpoint of PFS and achieved positive results with statistical significance and clinical benefit. The mPFS of the ivonescimab group was 11.14 months and the pembrolizumab group was 5.82 months (HR=0.51, P<0.0001). In 2025, this indication was approved for marketing in China.
Currently, the international multi-center phase III clinical study (HARMONi-7/AK112-3007) of ivonescimab monotherapy versus pembrolizumab in the first-line treatment of NSCLC with high PD-L1 expression is being carried out efficiently.
The HARMONi-2 study is the world's first randomized, double-blind, controlled phase III clinical study comparing pembrolizumab to achieve significant positive results in OS and PFS. Pembrolizumab is the most representative drug that ushered in the era of tumor immunotherapy 1.0. It has promoted major progress in the treatment of lung cancer and has become one of the most successfully commercialized innovative drugs in the world. On the basis of pembrolizumab, ivonescimab further brings significant benefits to patients, demonstrating the breakthrough clinical value and huge commercial value potential of ivonescimab as the next generation cornerstone drug of tumor immunity.
So far, ivonescimab has achieved positive OS and PFS results in multiple phase III clinical trials comparing head-to-head PD-1/L1 therapy, and has gradually expanded to major solid tumors other than lung cancer. The "tumor immunity + anti-angiogenesis" synergistic anti-tumor effect of ivonescimab has been continuously verified in clinical studies and the real world. ivonescimab therapy is expected to provide a more effective, safe and controllable new treatment option for cancer patients around the world, and promote the continued progress of cancer treatment.
About Yidafang® (PD-1/VEGF double antibody, ivonescimab)
Ivanescimab is the world's first PD-1/VEGF bispecific antibody independently developed by Akeso. It is the world's first new dual-antibody drug approved for marketing with a synergistic mechanism of "tumor immunity + anti-angiogenesis", leading a new wave of global tumor-immune dual-antibody development. Ivonescimab is also the first drug in the world to achieve positive results compared to the “king drug” pembrolizumab in a phase III study.
In the field of EGFR-TKI-treated advanced nsq-NSCLC where international PD-1/L1 monoclonal antibodies have not been approved, ivonescimab therapy became the first immunotherapy in the world to achieve clinical benefit and statistically significant double-positive results for OS and PFS with the Phase III HARMONi-A study; in the Phase III HARMONi-2 study, the PFS of ivonescimab in the first-line treatment of PD-L1-positive NSCLC was as long as 11.14 months, nearly double the 5.82 months of pembrolizumab in the control group, making ivonescimab the first drug in the world to achieve positive results compared with the "King of Drugs" in a phase III study; in the phase III HARMONi-6 study, ivonescimab combined with chemotherapy compared with tislelizumab combined with chemotherapy for the first-line treatment of squamous NSCLC, and achieved double-positive results for OS and PFS with significant clinical benefit and statistical significance.
These research results have established ivonescimab's global leading position as a cornerstone drug in the IO2.0 era, and proved that whether it is compared with PD-1 monotherapy, PD-1 + chemotherapy (currently the optimal SOC for many tumor treatments), or compared with VEGF therapy in the field of tumor anti-angiogenesis, ivonescimab therapy has significant clinical breakthroughs and strong iterative capabilities for existing therapies.
Based on the outstanding clinical value of ivonescimab in the field of IO2.0, the company is accelerating the construction of a global, all-tumor, and full-thread tumor therapy matrix with ivonescimab as the core, including it as the core component of the company's IO2.0+ADC2.0 strategy, and continues to promote the upgrading and iteration of the global treatment landscape for various major tumor types.
Currently, ivonescimab has conducted more than 16 Phase III clinical studies globally (6 of which are international multi-center registration Phase III clinical studies, and 7 are head-to-head PD-1/L1 therapies), including 8 registration/Phase III studies in the field of lung cancer, and first-line treatment of MSS/pMMR type colorectal cancer, first-line treatment of PD-L1-positive head and neck squamous cell carcinoma (combined with ligufalimab vs pembrolizumab), first-line treatment of biliary tract cancer (vs durvalumab therapy), first-line triple-negative breast cancer, first-line treatment of pancreatic cancer, first-line treatment of urothelial cancer (vs pembrolizumab+Nectin4 ADC) and other indications with significant value potential. In December 2022, Akeso licensed part of the overseas rights and interests of ivonescimab to the American Summit Company with a record-breaking plan of US$5 billion (US$500 million down payment) + 2-digit percentage sales commission + partner equity, leading the wave of Chinese new drugs going global.
About Akeso
Akeso (9926.HK) was established in 2012, adhering to the With the original intention of "developing the world's leading innovative drugs in China, allowing patients to be the first to benefit from the world's most advanced treatment options", relying on advanced dual-antibody/multi-antibody technology, the company successfully developed and launched the world's first bispecific antibody drugs cadonilimab (PD-1/CTLA-4 dual-antibody) and ivonescimab (PD-1/VEGF dual antibody) is the only pharmaceutical company in the world with two bispecific cancer immunotherapy drugs. It has opened the global era of immuno-oncology (IO) 2.0 and led a new wave of development of new international dual-antibody drugs. It has grown into a globally innovative and influential company.
Currently, the company has built a unique end-to-end comprehensive new drug research and development platform, using AI intelligent research to empower the entire process of drug development. Based on the advantages of dual-antibody/multi-antibody technology, the company has expanded its research and development territory to ADC/double-antibody ADC, TCE, siRNA, cell therapy, and mRNA. In other cutting-edge technology fields, more than 50 innovative drug candidates have been developed for the treatment of major diseases such as tumors, autoimmunity, respiratory system, central nervous system, inflammation, and metabolic diseases. Nearly 30 new drugs are in the clinical development stage (including 15 bispecific/multispecific antibodies and bispecific ADCs), 8 new drugs have been approved for commercialization, and 5 independently commercialized new drugs with a total of 12 indications have been included in the national medical insurance catalog.
In the field of oncology, Akeso is making every effort to promote the "IO2.0+" strategy and continue to promote the iterative upgrade of treatments for major oncology diseases.
Among them, ivonescimab is the first drug in the world to achieve positive results in a phase III study comparing the "king of drugs" pembrolizumab, and is also the first drug to achieve positive results in OS and PFS in a phase III clinical trial comparing PD-1 monoclonal antibody combined with chemotherapy, a trump card combination therapy in the IO1.0 era. At present, ivonescimab has achieved positive results in multiple registration/phase III studies. The indications for first-line PD-L1-positive non-small cell lung cancer and non-squamous non-small cell lung cancer with progress in EGFR-TKI treatment have been approved for marketing and included in medical insurance. First-line squamous non-small cell lung cancer has been approved for marketing. A total of 16 registration/phase III clinical trials of ivonescimab are ongoing, including 6 international multi-center registration/phase III clinical trials.
Cadonilimab is the world's first new bispecific cancer immunotherapy drug, which has filled many gaps in clinical and industrial fields and won the "China Patent Gold Award" from the State Intellectual Property Office. At present, cadonilimab has achieved positive results in multiple registration/phase III studies. The indications for first-line gastric cancer, first-line cervical cancer and recurrent/metastatic cervical cancer have been approved for marketing and included in medical insurance. A total of 13 registration/phase III clinical trials are being carried out, including 2 independent international multi-center registration/phase III clinical trials.
The IO2.0+ADC2.0 global strategy is an important layout for the company to create a therapeutic matrix with cross-generational competitive advantages. At present, ivonescimab/cadonilimab, as the cornerstone drug of IO2.0, has been jointly carried out with multiple self-developed new-generation bispecific ADCs/differentiated single-target ADCs, as well as high-potential ADC products from domestic and foreign companies such as GlaxoSmithKline, Pfizer, Biokin, and Yilian Biotech.
In addition to the field of oncology, the company also continues to promote the upgrading and iteration of treatment options in areas with major unmet clinical needs such as autoimmunity, respiratory and central nervous system diseases. A series of bisAb drugs with global breakthrough clinical value are in efficient clinical development, forming an echelon and complementing new drugs such as ebronucimab, ebdarokimab, and gumokimab that have been commercially sold.
International development is Akeso's core development strategy. Following the first in China to license the rights to independently developed CTLA-4 monoclonal antibody to Merck & Co. in 2015, the company licensed part of the overseas rights and interests of ivonescimab to Summit Therapeutics of the United States with a plan of "US$5 billion + 2-digit percentage sales commission + partner equity", setting a record for the foreign licensing of new drugs in China at that time. In addition, two indications of penpilimab for the treatment of nasopharyngeal carcinoma have been approved by the U.S. Food and Drug Administration (FDA).
Akeso hopes to develop new drugs that are the first in the world and the best treatments of its kind through efficient and breakthrough R&D innovation, provide better disease solutions to patients around the world, and become the world's leading biopharmaceutical company.