Translating What is Seen in Nonclinical Studies to Enhance Development into the Clinic
14.00 Understanding Clinical Trial Failures Through GBM PDX Models: Role of the Blood-BrainBarrier, Payload & Bystander Killing in Efficacy &
Toxicity of EGFR-targeting ADCs in Glioblastoma
- Using GBM PDX models, limited delivery across the blood-brain barrier (BBB) and development of resistance are the major reasons for the
failure of EGFR-targeting ADCs in clinical trials
- Using convection enhanced delivery method to deliver drugs directly to the brain tumors by passing the BBB
- Optimizing the toxin to be used as a payload on ADCs for GBM therapy, and understanding the role of bystander effects of released payload in determining efficacy and toxicity in GBM
Sonia Jain, Research Associate, Mayo Clinic
14.30 The Development & Characterization of an anti-Claudin-6 (CLDN6) Antibody-Drug Conjugate for the Treatment of CLDN6 Positive Cancer
- Outlining the high cancer specific expression of CLDN6 and how this makes it an ideal ADC target
- Sharing data generated from a selective ADC that is highly efficacious in CLDN6 positive models
- Overviewing IND-enabling studies that suggest the ADC will be tolerable clinically, and discussing that the ADC is currently in Phase I dose-escalation safety studies
Martina McDermott, Adjunct Assistant Professor, UCLA
