Enthusiasm for Akeso’s first-line non-small cell lung cancer data on ivonescimab, in partnership with Summit Therapeutics, has increased significantly after being featured in the plenary session of the upcoming ASCO 2026 Annual Meeting.
As the first Chinese development asset to earn this prime-time slot in the more than 60-year history of oncology events, ivonecimab will demonstrate overall viability in the Phase 3 Harmoni-6 trial. The study previously showed that the first-in-class PD-1xVEGF inhibitor, when used in combination with chemotherapy, outperformed BeOne Medicines’ PD-1 inhibitor Tevinbra and chemotherapy in progression-free survival (PFS) in Chinese patients with newly diagnosed squamous NSCLC.
But honor comes with scrutiny. Premier status means Harmoni-6’s results will be put under the microscope and carefully critiqued, Daina Graybosch, Ph.D., an analyst at Leerink Partners, said in an interview with Fierce previewing the published results.
“It would be completely chopped up,” Graybosh said. “That’s the risk of going to a plenary session. If you had the same data in a normal oral (session), there would be fewer critical discussants.”
Some expectations were so high ahead of the May 31 plenary session that one physician KOL bet a cup of coffee to Graybosch that ivonecicimab would report an overall survival improvement of more than 50%.
50% would be an impressive result that would “exceed everyone’s expectations,” Graybosh said. Even KOLs admit that it’s just a guess and aren’t really confident.
For now, even information about whether Harmoni-6 achieved statistical significance in terms of overall survival remains confidential. If successful, this would be the first regimen to demonstrate survival benefit over PD-1 plus chemotherapy in first-line NSCLC in a Phase 3 trial, meeting oncology’s gold standard for clinical efficacy.
There are two main camps of investors, Graybosch said.
When the Harmoni-6 results were first published in The Lancet, the statistical plan, which was clearly not properly edited, showed that the stopping boundary for an interim analysis of OS was a hazard ratio (HR) of 0.722. That is, if ivonescaimb showed a 27.8% OS improvement along with other criteria, the trial could claim success on the endpoint.
One group of investors believes that plenary participation is statistically significant and a better outcome than the effectiveness threshold. Therefore, they believe that ivonescimab will have an HR of 0.65 to 0.7.
The other half of investors still believe the data came from an unplanned, ad hoc analysis with no statistical significance, similar to what Akeso did with Harmoni-2 at the request of Chinese regulators. These investors are more pessimistic about the absolute magnitude of the effect, citing past research in the field of immuno-oncology, and suspect that ASCO selected this study for plenary because it originated in China, a rising biotech innovation, and is open to debate.
Following that logic, Graybosch’s team ran a simulation based on measurements of several recent immunotherapies in first-line NSCLC, some of which did not have the exact same squamous indication as Harmoni-6. Based on pooled PFS and overall response rate data, the estimated OS HR for Harmoni-6 would be approximately 0.83 and 0.87, according to Leerink’s calculations.
Nevertheless, Greybosch sided with the first group of investors in an April 21 memo, arguing that Plenary “likely achieved a significant OS benefit” by combining ivonecicimab with chemotherapy, with a statistically significant HR of better than 0.722 bars. But attention needs to be paid to more than just HR size, she argued. And even bullish KOLs are wary of focusing on top-line OS without context.
“I thought anything less than 0.7 would be a really big win, but the devil is in the details,” she said.
Leerink analysts said they will closely monitor whether patients receive appropriate subsequent treatment. This will be important in translating China-only Harmoni-6 results to a global population, as effective second-line treatments typically blunt the OS effects of first-line treatments.
“Our team notes that inadequate access to subsequent treatment is likely to impact early, premature OS analyses. As in this Harmoni-6 study, median follow-up is expected to be approximately 19 to 20 months,” the Graybosch team wrote in a May 27 note.
In an interview with Fierce, Graybosch initially suggested that HR was more important than absolute median OS length because HR helps estimate the world’s population. But she quickly changed her mind. This is because poor performance in the control arm may artificially enhance the therapeutic effect of ivonecicimab.
In the phase 3 Rationale-307 trial conducted in China in first-line squamous cell NSCLC, Tevinbra plus chemotherapy resulted in a median OS of 22.8 months. In the global Keynote-407 trial, conducted several years before the BeOne study, the combination of Keytruda and chemotherapy resulted in a median OS of 15.8 months at the interim analysis and 17.1 months at the final analysis.
The bullish KOL also cautioned that Harmoni-6 enrolled primarily Chinese male smokers, which could limit the translatability of the results to a more heterogeneous global population.
The stakes are even higher for Harmoni-6 after Akeso’s partner Summit recently effectively telegraphed that it surprisingly missed PFS during the interim analysis of the squamous epithelial cohort, as the global clinical trial of Harmoni-3 continues towards final PFS analysis. This update caught industry observers of the PD-(L)1xVEGF field by surprise, as Harmoni-6 had provisionally met PFS.
Assuming that the Harmoni-3 mistake implied a 10 percentage point reduction in the effect size of ivonecimab from China to the global population, Gravesock said the OS improvement metric for Harmoni-6 would be “reasonable” at 30% “in a really clean study” where patients received appropriate second-line therapy. Even a 20% improvement in world population could be statistically significant and meaningful, she said.
“But let’s say[the HR is]0.65. But there’s a lot of interesting business that the discussants pointed out, so it’s even less likely that this will go global. I think that’s where it’s hard to know what’s going to happen[with Harmoni-3].”
In addition to other PD-(L)1xVEGF bispecific drugs, ivonecicimab also currently faces competition from Merck & Co. and Kelun-Biotech’s sac-TMT. In the OptiTROP-Lung05 China study, the TROP2 antibody drug conjugate in combination with Keytruda improved PFS by 65% compared to Keytruda alone in first-line PD-L1-positive NSCLC, according to results to be presented at ASCO 2026.
Keytruda monotherapy is primarily used in the PD-L1-high population in the United States, so that is the only population that is important for a head-to-head comparison of ivonescimab/sac-TMT, Graybosch said. For now, only PFS data is available from the two regimens, but that’s not enough for a proper comparison, Graybosch said, as OS and toxicity are also important in assessing their potential.
Unlike Summit’s bold plan with Harmoni-3 to test ivonecicimab and chemotherapy against Keytruda and chemotherapy in the comprehensive first-line NSCLC setting, Merck’s strategy with sac-TMT is more targeted. The phase 3 TroFuse-023 trial combines Keytruda with sac-TMT in first-line maintenance therapy in squamous NSCLC. The TroFuse-007 trial focuses on the combo in PD-L1 high NSCLC.
Merck has disclosed little about its plans for its PD-1xVEGF drug, MK-2010. Graybosch suggested that Merck could conduct a study combining MK-2010 with sac-TMT and platinum chemotherapy against standard Keytruda chemotherapy in first-line non-squamous NSCLC, or with enhanced TROP2 biomarkers without the aid of additional chemotherapy.
“We think sac-TMT has best-in-class capabilities, but it’s also important to place it in the right tumor types and have the right strategy for those tumor types,” Merck Research Institute Director Dean Lee, MD, said on an investor conference call in February. “While there may be some tumor types where we don’t think a biomarker is needed, we think there are other places where it might be needed, especially given how good a comparator you need to compare it to.”
Meanwhile, Akeso and Summit investors find themselves caught in a contradiction. They hope Harmoni-6 will be a huge success at the ASCO plenary. This is also to validate the upcoming global announcement of Harmoni-3. However, as Graybosch pointed out, if the OS bar is set too high in this China-only cohort, there will only be downside risk from here.
