Vepdegestrant is an investigational oral PROTAC estrogen receptor degrader being developed by Arvinas and Pfizer for ESR1-mutated ER-positive/HER2-negative advanced or metastatic breast cancer after endocrine-based therapy. FDA accepted its NDA in August 2025 and set a PDUFA action date of June 5, 2026. It is not yet approved as of this filing stage.
FDA has accepted the NDA for vepdegestrant (ARV-471), an oral PROTAC ER degrader from Arvinas and Pfizer, for ESR1-mutated ER+/HER2- advanced breast cancer. A PDUFA date of June 5, 2026 has been set. The submission is based on positive Phase 3 VERITAC-2 data.
Recent developments in breast cancer treatment include new clinical trials for advanced disease, findings on CDK4/6 inhibitor sequencing, and discovery of genetic markers explaining drug resistance in HER2-positive breast cancer.
Proteolysis-targeting chimeras (PROTACs) are advancing from experimental to clinical-stage cancer therapies, with first candidates entering Phase III trials. The technology degrades target proteins rather than blocking them, offering new options for previously undruggable targets.
Pfizer reported positive Phase 3 trial results for BRAFTOVI combination therapy in metastatic colorectal cancer and received FDA Priority Review for HYMPAVZI expansion to hemophilia patients including children.
| NCT ID | Title | Status | Phase |
|---|---|---|---|
| NCT07231991 |
A Study to Learn How the Body Processes the Study Medicine Called Vepdegestrant in People With Loss of Liver Function |
RECRUITING | PHASE1 |
| NCT06275841 |
A Study to Learn If the Study Medicine Esomeprazole Changes How the Body Processes the Other Study Medicine Vepdegestrant |
COMPLETED | PHASE1 |
| NCT06256510 |
A Study to Learn If the Study Medicine Called Vepdegestrant Changes How the Body Processes the Other Study Medicine Called Midazolam |
COMPLETED | PHASE1 |
| NCT06206837 |
A Study to Learn About Vepdegestrant When Given With PF-07220060 to People With Advanced or Metastatic Breast Cancer. |
ACTIVE_NOT_RECRUITING | PHASE1/PHASE2 |
| NCT06125522 |
TACTIVE-U: A Study to Learn About the Study Medicine (Vepdegestrant) When Given With Other Medicines in People With Advanced or Metastatic Breast Cancer. (Sub-Study C) |
ACTIVE_NOT_RECRUITING | PHASE1/PHASE2 |
| NCT06005688 |
A Study to Understand the Effects of Carbamazepine on How Vepdegestrant is Processed in Healthy Participants |
COMPLETED | PHASE1 |
| NCT05538312 |
A Study to Understand the Effect of Itraconazole on the Levels of a Study Medicine Called ARV-471 in Healthy Adults |
COMPLETED | PHASE1 |
| NCT05463952 |
A Study to Learn About the Vepdegestrant (ARV-471, PF-07850327) in People With ER+/HER2- Locally Advanced or Metastatic Breast Cancer (BC) |
ACTIVE_NOT_RECRUITING | PHASE1 |
