George Zahrah

Aug 10, 2024 | cancernetwork.com | Erika Hamilton |Rinath Jeselsohn |Sara A. Hurvitz |Dejan Juric |Hyo S Han |Melinda L. Telli | +8 more

BackgroundVepdegestrant (ARV-471) is an oral proteolysis-targeting chimeras (PROTAC) estrogen receptor (ER) degrader. In a phase 1/2 study (NCT04072952), vepdegestrant monotherapy had a favorable safety profile and encouraging clinical activity with robust ER degradation. The phase 1b cohort of this study is evaluating vepdegestrant plus the CDK4/6inhibitor palbociclib.

Aug 4, 2024 | cancernetwork.com | Sara A. Hurvitz |Anne F. Schott |Cynthia X. MA |Rita Nanda |George Zahrah |Natasha Hunter | +10 more

BackgroundVepdegestrant (ARV-471) is an oral proteolysis-targeting chimeric (PROTAC) estrogen receptor (ER) degrader with activity toward wild-type and mutant ER. The phase 2 expansion (VERITAC) of a phase 1/2 study tested 2 vepdegestrant doses (200 mg once daily and 500 mg once daily) in heavily pretreated patients with ER+/HER2-negative (HER2–) advanced breast cancer.

Apr 27, 2023 | cancernetwork.com | Sara A. Hurvitz |Anne F. Schott |Cynthia X. MA |Erika Hamilton |Rita Nanda |Natasha Hunter | +11 more

BackgroundARV-471 is a selective, orally administered PROTAC protein degrader that targets wild-type and mutant ER1. ARV- 471 directly binds an E3 ubiquitin ligase and ER to trigger ubiquitination of ER and its subsequent proteasomal degradation. In contrast, selective estrogen receptor degraders (SERDs) indirectly recruit the ubiquitin-proteasome system, secondary to conformational changes and/or immobilization of ER2.