Nearly half of HER2-positive gastric cancer patients lose HER2 expression after initial chemotherapy and trastuzumab. This dynamic biomarker status requires re-testing at progression to confirm eligibility for subsequent HER2-targeted therapies like trastuzumab deruxtecan, ensuring the right patients receive the treatment.
The Horizon GA-01 trial's control arm became outdated mid-study when a superior standard of care (Keynote 811) was approved. This highlights a critical challenge in drug development: long trial timelines can conflict with rapid progress, making it difficult to compare new agents against the true contemporary standard.
Zolbituximab causes significant nausea and vomiting as a direct result of binding its Claudin 18.2 target in the stomach. Its clinical success depends on aggressively managing this on-target effect with prophylactic multi-drug antiemetics and adjusted infusion rates, particularly during the initial treatment cycle.
While the monoclonal antibody zolbituximab requires high Claudin 18.2 expression (>=75%), newer antibody-drug conjugates (ADCs) like AZD-091 are effective in patients with much lower expression (>=25%). This evolution in drug modality significantly broadens the eligible patient population for a given therapeutic target.