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A new antibody drug conjugate, GSK5764227 (also known as HS-20093), is showing early promise in clinical trials for HER2-expressing cancers, offering a potential new option for patients who’ve stopped responding to existing treatments. It’s a big deal as resistance and toxicity remain significant hurdles in HER2-targeted therapy.
GSK5764227 is an investigational treatment designed to overcome limitations of earlier HER2-targeted antibody-drug conjugates.
- GSK5764227 is being developed by GSK and Hansoh pharma.
- The drug utilizes a modern ADC architecture with a HER2-specific antibody, cleavable linker, and potent payload.
- Early clinical data suggest manageable safety and biological activity across multiple HER2-expressing tumor types.
- The ARTEMIS study is evaluating the drug’s safety, tolerability, and preliminary efficacy.
What makes GSK5764227 different? This next-generation antibody-drug conjugate (ADC) is engineered for improved tumor selectivity and payload delivery,aiming to minimize side effects while maximizing its impact on cancer cells.It’s a refinement of a strategy that’s already proven effective, but with a focus on addressing the shortcomings of earlier versions.
Molecular Design and How It Works
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GSK5764227, like many modern ADCs, has three key components: a monoclonal antibody specifically targeting HER2, a linker that can be cleaved to release the drug, and a highly potent cytotoxic payload. The antibody acts like a guided missile, binding to HER2 on tumor cells and bringing the drug inside.
Once inside the cell, the linker breaks down, releasing the payload which than damages the cell’s DNA or disrupts critical processes, ultimately leading to cell death. The design emphasizes a “controlled bystander effect,” meaning the drug can kill not only the targeted cell but also nearby cancer cells, even if they have lower levels of HER2.
Why This Matters: Unmet Needs in HER2-Positive Cancers
HER2-targeted therapies have revolutionized the treatment of certain cancers, notably breast and gastric cancers. However, resistance frequently develops, and existing treatments can cause significant side effects, like problems with blood counts or lungs. GSK5764227 aims to address these issues by optimizing the drug-to-antibody ratio, linker stability, and how the payload is released, perhaps improving effectiveness and reducing toxicity.
Early Trial Results: The ARTEMIS Study
The clinical progress of GSK5764227 is centered around the ARTEMIS study (NCT05276609), a phase 1 trial evaluating the drug in patients with advanced or metastatic HER2-expressing solid tumors. This first-in-human study is designed to assess safety, determine
