NMPA Approves Ivonescimab Plus Chemotherapy for First-Line Squamous NSCLC Based on HARMONi-6 Data

China's National Medical Products Administration (NMPA) has approved a supplemental New Drug Application (sNDA) for ivonescimab injection in combination with chemotherapy as a first-line treatment for advanced squamous non-small cell lung cancer (sq-NSCLC).¹ The approval marks the third lung cancer indication for ivonescimab, Akeso's PD-1/VEGF bispecific antibody, and is based on results from the Phase III HARMONi-6 (AK112-306) trial.¹

What did the HARMONi-6 trial show?

The randomized, double-blind trial enrolled 532 patients, including a population weighted toward more difficult-to-treat disease: approximately 63% had centrally located squamous tumors, 39.0% had PD-L1 tumor proportion scores below 1%, and 33.8% had multi-site, liver, or brain metastases.¹ Ivonescimab plus chemotherapy reduced the risk of death by 34% compared with tislelizumab plus chemotherapy (hazard ratio 0.66; 95% CI, 0.50-0.87; P=0.0017), with median overall survival of 27.9 months versus 23.7 months in the control arm.¹ The survival benefit widened over time: 12-month overall survival was 78.9% versus 72.2%, and 24-month overall survival was 64.7% versus 48.6%, for the ivonescimab and control arms, respectively.¹ At a prespecified interim analysis, the regimen also showed a statistically significant progression-free survival improvement, with a median of 11.1 months versus 6.9 months (hazard ratio 0.60; 95% CI, 0.46-0.78; P<0.0001).¹ Benefit was consistent across prespecified subgroups regardless of PD-L1 expression or metastatic burden, and the overall safety profile was comparable to the control arm.¹

The PD-1/VEGF bispecific mechanism is notable in this setting because anti-angiogenic agents have historically been avoided in squamous NSCLC: bevacizumab, the first approved anti-VEGF therapy for NSCLC, carries squamous histology as an absolute contraindication due to an elevated risk of fatal pulmonary hemorrhage observed in early trials.² Akeso says the ivonescimab regimen overcomes this longstanding limitation.¹ More recent analyses have questioned whether that historical caution remains warranted for newer antiangiogenic and bispecific approaches, citing comparatively low bleeding rates observed in more recent squamous NSCLC trials, including ivonescimab's own studies.³

Why does this data matter for the broader treatment landscape?

HARMONi-6's overall survival data were presented in a plenary session at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, marking the first time a China-originated novel oncology therapy has been featured in an ASCO plenary session, with full results simultaneously published in The Lancet.¹ The progression-free survival results were previously presented in a presidential symposium at the 2025 European Society for Medical Oncology (ESMO) Congress.¹ In a press release, professor Shun Lu, principal investigator of HARMONi-6 and director of the oncology department at Shanghai Chest Hospital, said, "We are highly encouraged by the dual-positive PFS and OS results from HARMONi-6 and proud to see the approval of ivonescimab plus chemotherapy for first-line sq-NSCLC. By outperforming PD-1 plus chemotherapy, this regimen has rewritten the gold standard of care and represents a landmark advance in the treatment of lung cancer."¹

What did company leadership say?

Xia Yu, PhD, founder, chairwoman, president, and chief executive officer of Akeso, said, "We are incredibly pleased by the approval of ivonescimab plus chemotherapy for first-line advanced squamous NSCLC. This approval marks a critical milestone in the development of next-generation immuno-oncology therapies worldwide. Currently, ivonescimab stands as the cornerstone of Akeso's IO2.0 + ADC2.0 strategy. We are advancing a portfolio of highly differentiated therapies that continue to elevate and reshape the global treatment landscape in major cancers such as lung and breast cancer. Together with Summit, we are committed to bringing the full value of ivonescimab to patients worldwide."¹

What is ivonescimab's broader regulatory track record?

This is ivonescimab's third lung cancer approval in China. The drug was previously approved for second-line treatment of EGFR-mutant NSCLC based on the HARMONi-A trial, and for first-line PD-L1-positive NSCLC based on HARMONi-2, where it delivered a median progression-free survival of 11.14 months compared with 5.8 months for pembrolizumab, marking the first drug to post a positive phase 3 result against that leading PD-1 therapy.¹ Ivonescimab is co-developed globally by Akeso and Summit Therapeutics.

References

1. Ivonescimab plus chemotherapy approved for first-line squamous NSCLC; HARMONi-6 establishes new gold standard in lung cancer treatment. News release. PR Newswire. August 12, 2026. Accessed August 12, 2026.
2. Russo AE, Priolo D, Antonelli G, Libra M, McCubrey JA, Ferraù F. Bevacizumab in the treatment of NSCLC: patient selection and perspectives. Lung Cancer (Auckl). 2017;8:259-269. doi:10.2147/LCTT.S110306
3. Pabani A, West H, Abu Rous F. Safety and efficacy of antiangiogenesis agents in patients with squamous cell carcinoma of the lung: time to revise outdated constraints. JCO Oncol Adv. 2024;1(1):e2400089. doi:10.1200/OA-24-00089