Challenges in maintaining uniform performance for a competitor of Keytruda, Summit's cancer drug, surface across multiple locations, fueling doubts about potential U.S. approval.

In a significant development for cancer therapy, Summit Therapeutics' investigational antibody, ivonescimab, has shown promising results in the Phase III HARMONi study. The drug, which blocks both the PD-1 and VEGF pathways, has demonstrated a statistically significant survival benefit in patients with advanced non-small cell lung cancer (NSCLC).

The region with the highest number of patients in the HARMONi study where ivonescimab showed a survival benefit was China. Approximately two thirds of the global HARMONi trial population came from the Harmoni-A trial conducted in China, which demonstrated a significant overall survival advantage. However, geographical inconsistencies in ivonescimab's efficacy have come under scrutiny, with the overall survival benefit being 24% in Asian patients and 16% in the Western subgroup (North America and European countries).

In North American patients specifically, median overall survival had not yet been reached at the time of read out, while in Western patients, ivonescimab, when combined with chemotherapy, resulted in a median overall survival of 16.8 months, versus 14 months in comparators on placebo plus chemotherapy. The benefit of ivonescimab was demonstrated to be consistent across different patient groups, including Western and Asian patients, with at least six months of follow-up.

PFS, or progression-free survival, is a co-primary endpoint of the Phase III study for ivonescimab. In the trial, ivonescimab, when combined with chemotherapy, cut the risk of disease progression or death by 43%, according to progression-free survival data provided by Summit.

Despite these promising results, the regulatory path for Ivonescimab in EGFR-mutant lung cancer remains uncertain, and reliant on an act of leniency by the FDA. Summit intends to file a Biologics License Application for ivonescimab, though no explicit announcement has been made in recent news releases.

Tristan Manalac is the reporter for this article, and can be contacted via LinkedIn, email, or through the provided website.

In May, Summit announced that ivonescimab had missed its overall survival target in the trial. However, the company is hopeful that the significant PFS benefit and consistent survival advantage across different patient groups will be enough to secure marketing authorization for ivonescimab.

As we wait for further developments, it is clear that ivonescimab has the potential to be a game-changer in the treatment of advanced NSCLC, particularly in combination with chemotherapy. The FDA has stated that a statistically significant overall survival benefit is necessary to support marketing authorization for ivonescimab in the U.S., and it will be interesting to see how this plays out in the coming months.