RESEARCH AND DEVELOPMENT | ONCOLOGY
RESEARCH AND DEVELOPMENT | ONCOLOGY
Oncology
Arvinas is advancing the discovery and development of PROteolysis-TArgeted Chimeras (PROTAC) protein degraders as a new class of potential cancer therapies. Many oncogenic drivers have historically been considered “undruggable,” limiting treatment options for patients. PROTAC protein degraders offer a fundamentally different approach by harnessing the cell’s own protein disposal system to eliminate disease-causing proteins rather than simply inhibiting them. Arvinas is applying this novel technology across a range of cancers, with the goal of delivering transformative, targeted therapies for patients with high unmet medical need.
Vepdegestrant: a PROTAC Estrogen Receptor Degrader for Breast Cancer *
Arvinas and Pfizer are collaborating to develop and commercialize vepdegestrant, an investigational PROTAC estrogen receptor degrader administered orally for the treatment of patients with estrogen receptor (ER) positive / human epidermal growth factor receptor 2 (HER2) negative (ER+/HER2-) locally advanced or metastatic breast cancer.
The U.S. Food and Drug Administration (FDA) is reviewing and has filed the New Drug Application (NDA) for vepdegestrant for its use as a monotherapy in the treatment of adults with ER+/HER2- ESR1-mutated advanced or metastatic breast cancer previously treated with endocrine-based therapy. The FDA has assigned a Prescription Drug User Fee Act (PDUFA) action date of June 5, 2026. Vepdegestrant was granted Fast Track designation in February 2024 by the FDA, underscoring the significant unmet need in this patient population and the potential for vepdegestrant to offer a meaningful new treatment option.
Vepdegestrant is currently under investigation. The safety and effectiveness of vepdegestrant have not been established.
*In September 2025, Arvinas and Pfizer announced their plan to jointly select a third party for the out-licensing and commercialization of vepdegestrant.
Preclinical Studies
In preclinical studies, vepdegestrant demonstrated up to 97% ER degradation in tumor cells, induced robust tumor shrinkage when dosed as a single agent in multiple ER-driven xenograft models, and showed increased anti-tumor activity compared to fulvestrant, both as a single agent and in combination with CDK4/6 inhibitors. Vepdegestrant is a PROTAC that directly recruits the ubiquitin proteasome system to degrade the ER.
Clinical Oncology Pipeline Programs
Mechanism of Action:
ARV-393 is an investigational oral PROTAC degrader of BCL6, a transcriptional regulator that has long been considered “undruggable.” By degrading BCL6, ARV-393 aims to disrupt oncogenic signaling pathways that drive tumor cell survival and proliferation.
Clinical Status:
ARV-393 is currently being evaluated in a Phase 1 monotherapy trial in patients with relapsed or refractory NHL (NCT06393738).
Mechanism of Action:
ARV-806 is an investigational PROTAC degrader of KRAS G12D, one of the most common and historically “undruggable” oncogenic mutations across cancer types. By targeting the KRAS G12D protein for elimination rather than inhibiting its activity, ARV-806 aims to directly block oncogenic signaling and disrupt pathways that drive tumor growth and survival.
Clinical Status:
ARV-806 is currently being evaluated in a Phase 1/2 clinical trial in patients with advanced solid tumors harboring KRAS G12D mutations (NCT07023731).
- Lumachi, Santeufemia, Basso. Current medical treatment of estrogen receptor-positive breast cancer. World J Biol Chem. 2015 August 26;6(3) 231-239.
- Flanagan et al. SABCS 2018
- The et al. Enhanced efficacy of vepdegestrant (ARV 471), a novel PROTAC® estrogen receptor degrader, in combination with targeted agents in ER+ breast cancer models. AACR 2023
- Hormone Therapy for Breast Cancer was originally published by the National Cancer Institute.