Tanja Obradovic, Therapeutic Strategy Lead of Oncology at Novotech, Senior Advisor of Oncology Drug Development at HopeAI, shared a post on LinkedIn:
“2026 World Conference on Lung Cancer delivered excitement as read-out of overall survival (OS) for HARMONi-2 trial was presented and ivonescimab results were superior to pembrolizumab (Keytruda).
HARMONi-2 was a randomized, double-blind Phase III trial conducted in China comparing ivonescimab (PD-1/VEGF bispecific antibody) versus pembrolizumab monotherapy in treatment-naïve patients with advanced PD-L1-positive NSCLC without EGFR or ALK alterations.
At the August 20, 2026, data cutoff, 234 overall survival events had occurred. Median overall survival was 30.8 months with ivonescimab compared with 22.6 months with pembrolizumab (HR, 0.73; 95% CI, 0.57-0.95; P=0.009), representing a statistically significant survival benefit.
Bottom line, absolute OS gain with: ~8.2 months with ivonescimab compared to pembrolizumab. The largest benefit appeared to occur in patients with high PD-L1 expression (TPS ≥50%) that may be pointing to some underlying biological reasons for these results. There has been hypothesis behind ivonescimab MOA that the VEGF-binding arm may help localize the molecule to VEGF-rich tumor tissue, potentially increasing PD-1 blockade where it is most needed.
HARMONi-2 was single country Phase III trial in China. Despite these outstanding reported OS results it is unlikely that FDA will proceed to approval without global confirmatory data. Treatment approaches and patient population inevitably have specifics in each country/region as
- lifetime habits
- epidemiology
- medical practice
- healthcare resources
- coverage
are reflection of evolution in these and other areas within country or region.
Global clinical trials are critical to reveal applicability across patient populations and practices.
Lesson 1:
Biology matters. Likely mechanism of VEGF-guided preferential PD-1-blocking activity where T cells are interacting with tumor cells points to need to critically think about underlying tumor pathophysiology when thinking about combination regimen for Ab, ADCs or cell therapy.
Lesson 2:
Global strategy matters. While tempting to proceed into PhII and PhIII quickly within single large country, that path is ultimately longer and costlier than going global if desired destination of the launch includes that country plus other multiple markets.
Lesson 3:
Early communication to medical community matters. While Biotech investment community closely follows ex-USA assets and companies, global medical and patient community is not that fast to catch up and can benefit from much stronger global medical communication by emerging Biotech. Large Pharma has deep and wide global KOLs network as well as big marketing and communication campaigns, so Biotech needs to accel in using communication platforms early.
Lesson 4:
Who is advising on next step matters. If asset needs global expansion, addressing only medical aspect of planning with advisors/internal team is not sufficient. Including translational science and very importantly strategic pharmaceutical business acumen with proven global filing and launch background can lead to much better and faster path forward.
Sometimes guiding new drug during oncology clinical development can feel like going through hurricane.
Adding to that need to beat one of the most successful therapies of the last several decades certainly asks for continuous understanding and learning from the rapidly evolving data reports and fates of numerous ongoing trials.”
Read the full article.
Article: Ivonescimab versus pembrolizumab for PD-L1-positive non-small cell lung cancer (HARMONi-2): a randomised, double-blind, phase 3 study in China
Authors: Anwen Xiong, Lei Wang, Jianhua Chen, Lin Wu, Baogang Liu, Jun Yao, Hua Zhong, Jie Li, Ying Cheng, Yulan Sun, Hui Ge, Jifang Yao, Qin Shi, Ming Zhou, Bolin Chen, Zhengxiang Han, Jinliang Wang, Qing Bu, Yanqiu Zhao, Junqiang Chen, Ligong Nie, Gaofeng Li, Xingya Li, Xinmin Yu, Yinghua Ji, Daqiang Sun, Xiaohong Ai, Qian Chu, Yu Lin, Jiqing Hao, Dingzhi Huang, Chengzhi Zhou, Jinlu Shan, Hongzhong Yang, Xuewen Liu, Jing Wang, Yanhong Shang, Xiaodong Mei, Jie Yang, Dongmei Lu, Mingxiu Hu, Zhongmin Maxwell Wang, Baiyong Li, Michelle Xia, Caicun Zhou
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