Summit's Ivonescimab Nears Critical Phase III Data in Battle Against Keytruda

Summit Therapeutics is approaching a pivotal moment in its quest to challenge Merck's blockbuster cancer drug Keytruda, as the first global Phase III trial results for its bispecific antibody ivonescimab are expected in mid-2025. This milestone comes as the pharmaceutical industry intensifies its focus on developing next-generation cancer treatments that could potentially surpass the efficacy of established checkpoint inhibitors.

Ivonescimab's Progress and Potential

Ivonescimab, a PD-1/VEGF bispecific antibody, has already shown promise in Chinese trials conducted by Summit's partner Akeso. In September 2024, the drug demonstrated a 49% reduction in the risk of disease progression or death compared to Keytruda in first-line non-small cell lung cancer (NSCLC) treatment. This impressive performance led to ivonescimab's approval in China for a subset of NSCLC patients who progressed after tyrosine kinase inhibitor (TKI) therapy in May 2024, with a broader label expansion for first-line NSCLC patients following in April 2025.

However, recent interim overall survival (OS) data from Akeso's trials has sparked debate among analysts. While ivonescimab showed a 22.3% reduction in the risk of death compared to Keytruda, the difference did not reach statistical significance. This outcome has intensified interest in the upcoming global Phase III results, which will provide crucial insights into ivonescimab's potential to replicate its Chinese trial success on a global scale.

Industry Competition Heats Up

The race to develop improved cancer treatments has attracted significant attention and investment from major pharmaceutical companies. BioNTech acquired its PD-L1xVEGF bispecific partner Biotheus for $800 million, while Merck invested $588 million in a partnership with LaNova Medicines to enter the field. These moves underscore the industry's recognition of the potential market value, which Summit estimates at over $90 billion.

BioNTech has initiated a Phase II/III trial of its candidate BNT327 in first-line NSCLC, with potential advantages in half-life and target specificity compared to ivonescimab. Merck, not content to rest on Keytruda's success, has also entered the clinic with LM-299, emphasizing the potential for combination therapies with its existing portfolio.

The competition extends beyond bispecific antibodies, with antibody-drug conjugates (ADCs) like Daiichi Sankyo and AstraZeneca's Datroway presenting alternative approaches to improving cancer treatment. As these various modalities progress through clinical development, the landscape of cancer therapy could see significant shifts in the coming years.

Looking Ahead: Challenges and Opportunities

As Summit approaches its crucial data readout, the company faces both opportunities and challenges. The potential loss of Keytruda's exclusivity in 2028 could open the door for biosimilar competition, complicating the market dynamics for new branded treatments. Additionally, the need to demonstrate clear overall survival benefits and confirm efficacy in global studies remains a critical hurdle for ivonescimab and its competitors.

The mid-2025 readout of Summit's global Phase III trial in post-TKI NSCLC patients will be a key indicator of ivonescimab's potential to disrupt the current treatment paradigm. As the industry awaits these results, ongoing research into combination therapies and expansion into other cancer indications continues to drive innovation in the field.

With billions of dollars at stake and the potential to improve outcomes for thousands of cancer patients, the development of next-generation cancer treatments remains a focal point of pharmaceutical research and investment. The coming months and years will likely bring further developments that could reshape the landscape of cancer therapy and challenge the dominance of established treatments like Keytruda.