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vepdegestrant + PF-07220060

Development stage: Unknown
Lead developer: Pfizer
Modality: PROTACs (E3 ligase recruitment) → Targeted Protein Degraders (TPDs) → Small Molecules, Bivalent/Multivalent Binders → Multivalent & Scaffold-Based Small Molecules → Small Molecules
Administration: Oral

Overview

Vepdegestrant + PF-07220060 is an investigational, oral, fixed-combination therapy being evaluated for the treatment of estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer. Vepdegestrant (ARV-471, PF-07850327) is a proteolysis-targeting chimera (PROTAC) that selectively targets the estrogen receptor (ER) for degradation, thereby antagonizing estrogen-driven tumor growth. PF-07220060 (atirmociclib) is a highly potent, selective inhibitor of cyclin-dependent kinase 4 (CDK4), which blocks phosphorylation of the retinoblastoma (Rb) protein to prevent G1-to-S phase cell cycle progression. The combination aims to overcome resistance to prior endocrine and CDK4/6 inhibitor therapies, with enhanced anti-tumor efficacy observed in preclinical breast cancer models. Both components are administered orally and studied in ongoing phase 1b/2 clinical trials in patients with advanced ER+/HER2- breast cancer after progression on prior therapies[5][7][1].

Other names: vepdegestrant + atirmociclib

Targets

CRBN (Cereblon)CDK4 (Cyclin-dependent kinase 4)ER (Estrogen receptor)

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