Summit's Ivonescimab Shows Mixed Results in Global Phase III Trial

Summit Therapeutics' PD-1xVEGF bispecific antibody ivonescimab has demonstrated promising results in a global Phase III trial, despite missing one of its co-primary endpoints. The trial, known as HARMONi, evaluated ivonescimab in patients with EGFR-mutated, locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) who had progressed on a third-generation tyrosine kinase inhibitor.

Progression-Free Survival Success and Overall Survival Shortfall

The HARMONi trial met its co-primary endpoint of progression-free survival (PFS), with ivonescimab reducing the risk of disease progression or death by 48% compared to placebo when added to platinum-doublet chemotherapy. This result provides the first evidence that global pivotal trials of ivonescimab can reproduce the impressive efficacy previously shown in China.

However, the trial fell short on its other co-primary endpoint of overall survival (OS). While the OS data favored ivonescimab, it did not reach statistical significance. This mixed outcome has raised questions about the drug's potential for approval in the United States, where the FDA has indicated that a statistically significant OS benefit is necessary to support approval.

Analyst Optimism and Market Response

Despite the mixed results, analysts at Truist Securities remain optimistic about ivonescimab's potential. They noted that the similarity between Eastern and Western patient populations in the trial suggests that data generated for ivonescimab in China could be reproducible in Western populations.

The market response, however, was less enthusiastic. Summit's shares fell 15% to $22.25 in premarket trading following the announcement of the trial results.

Regulatory Landscape and Future Plans

Summit Therapeutics still plans to file for FDA approval of ivonescimab, though the company acknowledged that it would need to "consider the timing of the filing." The company emphasized that there are currently no FDA-approved regimens that have demonstrated a statistically significant overall survival benefit in this specific patient setting.

The HARMONi trial results come on the heels of ivonescimab's recent approval in China for first-line treatment of certain NSCLC patients. Summit is also conducting two additional Phase III trials comparing ivonescimab to Merck's Keytruda in first-line NSCLC, targeting patients with varying levels of PD-L1 expression.

As the pharmaceutical industry closely watches the development of PD-1/L1xVEGF bispecifics, Summit's global Phase III readout on ivonescimab represents a significant step toward understanding the potential of this novel class of drugs in both Eastern and Western markets.