NECTIN-4 PET FOR OPTIMIZING ENFORTUMAB VEDOTIN DOSE-RESPONSE IN UROTHELIAL CARCINOMA
2024

Using PET Imaging to Optimize Dosing of Enfortumab Vedotin in Bladder Cancer

publication Evidence: high

Author Information

Author(s): Mishra Akhilesh, Sharma Ajay Kumar, Gupta Kuldeep, Banka Dhanush R., Johnson Burles A., Hoffman-Censits Jeannie, Huang Peng, McConkey David J., Nimmagadda Sridhar

Primary Institution: Johns Hopkins University School of Medicine

Hypothesis

Can positron emission tomography (PET) imaging improve the understanding of antibody-drug conjugate pharmacology and optimize dosing strategies for enfortumab vedotin in urothelial carcinoma?

Conclusion

The study shows that PET imaging can effectively quantify target engagement and optimize dosing strategies for enfortumab vedotin, leading to improved therapeutic outcomes.

Supporting Evidence

  • PET imaging revealed dose-dependent variations in Nectin-4 engagement.
  • Target engagement measured by PET was a more reliable predictor of therapeutic efficacy than dose or baseline Nectin-4 expression alone.
  • Receiver operating characteristic analysis identified a target engagement threshold that is determinant of response.

Takeaway

This study uses a special imaging technique to see how well a cancer drug works in real-time, helping doctors give the right amount of medicine to patients.

Methodology

The study utilized Nectin-4-targeted PET imaging with [68Ga]AJ647 to assess target engagement and correlate it with therapeutic outcomes in preclinical models.

Limitations

The study does not fully account for the contribution of the cytotoxic payload to therapeutic outcomes, which can complicate the interpretation of results.

Statistical Information

P-Value

p<0.0001

Statistical Significance

p<0.0001

Digital Object Identifier (DOI)

10.1101/2024.12.25.630315

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