Akeso’s ivonescimab beats Keytruda on overall survival in China as Summit Therapeutics’ global wager gains another proof point

Akeso Inc. (HKEX: 9926) has reported that ivonescimab significantly improved overall survival compared with Merck & Co., Inc.’s Keytruda, or pembrolizumab, in the Phase III HARMONi-2 trial involving previously untreated patients with PD-L1-positive advanced non-small cell lung cancer. Median overall survival reached 30.8 months with ivonescimab versus 22.6 months with pembrolizumab, corresponding to a hazard ratio of 0.73 and a 27% reduction in the risk of death at the interim analysis. The study had already demonstrated median progression-free survival of 11.1 months versus 5.8 months, and the new survival readout substantially strengthens the clinical importance of that earlier result. The major unresolved question is geographic: HARMONi-2 enrolled patients in China, while Summit Therapeutics Inc. (Nasdaq: SMMT) needs its separate global programme to establish whether the benefit translates across the markets where it holds commercial rights.

The trial enrolled 398 patients, with 198 receiving ivonescimab and 200 receiving pembrolizumab. At the August 20, 2026 data cutoff, 234 deaths had occurred and median follow-up was approximately 36 months. Akeso said the survival improvement met the prespecified statistical threshold, making HARMONi-2 the first randomised double-blind Phase III study reported by the company to show statistically significant improvements in both progression-free survival and overall survival against pembrolizumab in this setting.

Why is beating pembrolizumab on overall survival more important than another positive oncology response rate?

Pembrolizumab has become one of the defining oncology products of the immunotherapy era and generated $8.37 billion of sales for Merck & Co., Inc. in the second quarter of 2026 alone, including Keytruda Qlex. Demonstrating a response rate or even a progression-free survival advantage over such an established therapy would attract attention, but overall survival provides a more consequential measure because it addresses whether patients actually live longer.

Ivonescimab combines inhibition of PD-1 with blockade of VEGF-A in a single bispecific antibody. The scientific rationale is to combine immune activation with an anti-angiogenic effect while potentially concentrating cooperative binding within the tumour microenvironment. Akeso’s HARMONi-2 data suggest that this mechanism can generate a clinically measurable survival advantage in the studied population rather than merely shrinking tumours more frequently.

The result does not mean ivonescimab has displaced Keytruda globally. HARMONi-2 was conducted in China, treatment standards and patient characteristics can differ between regions, and regulators outside China will evaluate data relevant to their own populations and submissions. The commercial thesis therefore moves from proving that ivonescimab can beat pembrolizumab somewhere to establishing whether it can do so consistently across international Phase III programmes.

Why does HARMONi-2 matter so much to Summit Therapeutics rather than only Akeso?

Summit Therapeutics licensed ivonescimab from Akeso in a transaction that has become one of the most important China-to-Western-biotech deals in oncology. Summit made an original $500 million upfront commitment, including cash and equity consideration, and subsequently paid another $15 million when the licensed territories were expanded to Latin America, the Middle East and Africa. Akeso can receive up to an additional $4.555 billion of regulatory and commercial milestones, together with low double-digit royalties on net sales in Summit’s licensed territories.

That structure explains why each major ivonescimab readout has unusually high financial relevance for Summit. The company is fundamentally built around turning Akeso’s molecule into a globally approved oncology franchise, and its future economics depend disproportionately on successful regulatory development and commercialisation. Akeso retains rights in markets outside Summit’s licensed territories, while Summit controls commercial strategy, pricing and reimbursement in regions including the United States, Canada, Europe and Japan.

Summit shares closed at $17.55 on September 11 after gaining 3.24% for the session and had risen materially during the preceding two weeks. That market strength preceded the full WCLC presentation, so any September 14 movement should be interpreted against an investment thesis already heavily influenced by expectations around ivonescimab rather than attributed mechanically to one conference release.

What global trials must now confirm before ivonescimab can challenge Keytruda commercially?

HARMONi-7 is particularly important because it directly evaluates ivonescimab against pembrolizumab in patients with high PD-L1 expression in an international setting. Summit is also running the HARMONi-3 programme in first-line non-small cell lung cancer, while additional studies are testing the molecule across other lung cancer and solid-tumour settings. The breadth matters because a single successful China study can establish strong biological evidence, but a global franchise requires reproducible efficacy, manageable safety and regulatory acceptance across multiple populations.

Summit’s filings indicate that enrolment in the non-squamous cohort of HARMONi-3 was completed during the second quarter of 2026, with the progression-free survival analysis expected in the first half of 2027. The company has also expanded ivonescimab into combination studies with treatments from Revolution Medicines, GSK and Arcus Biosciences.

The strategic opportunity is correspondingly large. If global data confirm that simultaneous PD-1 and VEGF blockade can consistently outperform established PD-1 monotherapy, ivonescimab could become more than another lung cancer drug and potentially influence how the next generation of immuno-oncology combinations is designed. Failure to reproduce the China data internationally would create the opposite conclusion, making HARMONi-2 an impressive regional result rather than proof of a universally superior treatment architecture.

What are the next measurable proof points for Akeso and Summit Therapeutics?

The immediate event is the full HARMONi-2 presentation at the 2026 World Conference on Lung Cancer, where subgroup, safety and longer-term data can be examined in greater detail. Beyond the conference, Summit’s global trials will carry more weight for the US and European investment thesis than further China-only studies because they are designed to support regulatory submissions in the territories where Summit owns commercial rights.

Regulatory progress is already advancing in another ivonescimab indication. Summit has disclosed a November 14, 2026 Prescription Drug User Fee Act target date for a US application involving ivonescimab combined with chemotherapy in previously treated EGFR-mutated non-squamous non-small cell lung cancer. That application addresses a different treatment setting from HARMONi-2, but approval would establish the molecule commercially in the United States while larger first-line trials continue.

HARMONi-2 therefore strengthens the scientific thesis without completing the commercial one. The most important evidence now is whether Summit can reproduce Akeso’s advantage in global populations and convert the extensive licensing commitment into approvals across large first-line cancer markets.

Key takeaways from Akeso’s HARMONi-2 ivonescimab results

• HARMONi-2 compared ivonescimab directly with pembrolizumab in first-line PD-L1-positive advanced NSCLC.
• Median overall survival was 30.8 months with ivonescimab versus 22.6 months with pembrolizumab.
• Ivonescimab reduced the risk of death by 27% at the interim analysis.
• Previous HARMONi-2 data showed median progression-free survival of 11.1 months versus 5.8 months.
• The trial enrolled 398 patients in China.
• Akeso already has Chinese approval for ivonescimab in this treatment setting.
• Summit Therapeutics owns development and commercial rights across major international markets.
• Akeso is eligible for up to $4.555 billion of additional milestones plus royalties from Summit.
• HARMONi-2 does not substitute for Summit’s global Phase III evidence.
• HARMONi-7 and other international studies are central to determining the drug’s global competitive potential.