Key Takeaways:
Akeso and Summit Therapeutics' ivonescimab reduced the risk of death by 34% in a Phase 3 trial for first-line advanced squamous non-small cell lung cancer, marking the first time a PD-1 inhibitor combination has beaten the standard of care in overall survival.
"The study provides a vital new path forward for patients with these difficult-to-treat cancers who have limited treatment options," David Spigel, president and chief medical officer at Sarah Cannon Research Institute, said in an ASCO release.
The HARMONi-6 trial enrolled patients in China and compared ivonescimab plus chemotherapy against BeOne Medicines' Tevimbra (tislelizumab) plus chemo. Median overall survival reached 27.9 months in the ivonescimab arm versus 23.7 months in the control group, a gain of 4.2 months. The p-value of 0.0017 exceeded the prespecified statistical significance boundary of 0.0049. The benefit appeared consistent across PD-L1 subgroups, with a 36% risk reduction in PD-L1-negative patients and 32% in PD-L1-positive patients.
The result positions ivonescimab as a potential challenger to Merck's Keytruda, which generated more than $20 billion in annual sales and faces patent expiration in 2029. Summit has already submitted an FDA application for ivonescimab as a later-line NSCLC treatment, and positive HARMONi-6 data could support expansion into first-line therapy, a much larger patient population. BMO Capital Markets analysts said the readout "could start to change the narrative around immuno-oncology in NSCLC."
A historic win with caveats
The 34% improvement exceeded many expectations, with some analysts skeptical the trial would meet statistical significance. The result also marks the first time a China-only data set was selected for ASCO's plenary session. However, Julie Brahmer, director of the thoracic oncology program at Johns Hopkins' Sidney Kimmel Comprehensive Cancer Center and the ASCO-invited discussant, raised concerns about the trial's applicability to global patients.
Brahmer noted that HARMONi-6 excluded patients older than 75 years, and in individuals older than 65, ivonescimab plus chemotherapy "failed to benefit" patients, with a hazard ratio near 1. The trial also enrolled almost exclusively men, whereas squamous NSCLC trials typically include at least 20% women. Brahmer said the eligibility criteria around tumor vascular invasion and hemoptysis risk create uncertainty for practicing oncologists deciding which patients to treat.
"Right now, I would say no, it's not applicable to the global patient population," Brahmer said. "We really do need that next wave of Harmoni studies."
The PD-1xVEGF race heats up
Ivonescimab is a bispecific antibody targeting both PD-1 and VEGF, blocking checkpoint inhibition while preventing tumor angiogenesis. The dual mechanism has attracted deep-pocketed rivals. Bristol Myers Squibb and BioNTech partnered in a deal valued at up to $11 billion to develop pumitamig, with Phase 2/3 data in first-line NSCLC also presented at ASCO. Pfizer is developing PFE-08634404, and AbbVie recently paid $650 million upfront plus up to $4.95 billion in milestones for RemeGen's ABBV-1480.
The VEGF component of ivonescimab solved a longstanding restriction: standalone VEGF inhibitors like bevacizumab are prohibited in squamous NSCLC due to bleeding risks. Grade 3 or above hemorrhages occurred in 2.6% of ivonescimab patients versus 0.8% in the control arm. But Brahmer said she saw little difference in VEGF-specific adverse events compared with historical anti-VEGF drugs.
For Summit Therapeutics, the data represents a major value inflection point. The company's shares have been closely tied to ivonescimab's trajectory since licensing the asset from Akeso. The next catalyst is the FDA's review of the later-line NSCLC application, with a decision expected in the coming months. Akeso will also need to launch global confirmatory trials to address questions about the China-only data set before regulators outside China will approve the drug for first-line use.
This article is for informational purposes only and does not constitute investment advice.
