Bispecific upstages Keytruda

The new bispecific drug ivonescimab has outperformed Mercks blockbuster PD-1 checkpoint inhibitor Keytruda (pembrolizumab) in a head-to-head clinical trial of non-small-cell lung cancer. The dual-action VEGFPD-1 antibody nearly doubled progression-free survival over the PD-1 blocker, according to phase 3 data presented by Summit Therapeutics at the World Conference on Lung Cancer in San Diego in September. Patients treated with ivonescimab survived without progression for a median of 11 months, compared with 5.8 months for patients in the Keytruda monotherapy arm. These results from 400 patients were better than expected, but this is a China-only trial and unlikely to support a US Food and Drug Administration filing. Several US trials are planned or underway.

Ivonescimab is a humanized tetravalent bispecific antibody that targets PD-1 and vascular endothelial growth factor (VEGF) simultaneously. The rationale for combining a PD-1-inhibitor to stop tumor immunosuppression with blockade of tumor angiogenesis is not new, but VEGF inhibitors can cause severe bleeding and checkpoint inhibitors are linked to immune-related toxicities. By having both binding domains on a single antibody, ivonescimab was able to avoid these side effects, and although it had some VEGF-related adverse events such as hypertension, there was no increased risk of hemorrhage.

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