Company: ARVN
Filing Date: 2025-02-11
Form Type: 10-K
Source: 0001655759-25-000016
Chunk: 99

Company: ARVINAS, INC.
Filing Date: 2025-02-11
Form: 10-K
Item: Item 1
Chunk 99
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 relative to fulvestrant in combination palbociclib or fulvestrant in combination with ribociclib, respectively, as shown in the figures below. 

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We believe that vepdegestrant also has the potential to show compelling activity in combination with other targeted agents currently used or in clinical trials for locally advanced or metastatic breast cancer including PI3K and mammalian target of rapamycin inhibitors and have tested and plan to continue to test these combinations in preclinical models. 

In the second quarter of 2023, we presented vepdegestrant preclinical data at the American Association for Cancer Research annual meeting that demonstrated the potential utility of vepdegestrant as an endocrine therapy backbone for combination with other targeted agents in early and late-stage ER+/HER2- breast cancer and the potential mechanisms of acquired resistance to vepdegestrant that may be associated with alterations within Receptor Tyrosine Kinase/MAPK signaling pathways rather than ER signaling or E3 ligase machinery.

In the fourth quarter of 2024, we presented vepdegestrant preclinical data at the San Antonio Breast Cancer Symposium, or SABCS, including vepdegestrant plus CDK4/6 inhibitor combinations in palbociclib-resistant patient derived xenograft, or PDX, models. In one PDX model harboring an ESR1 mutation (Y537S), vepdegestrant demonstrated anti-tumor activity as a single agent as well as enhanced activity in combination with abemaciclib, ribociclib or palbociclib compared to single agents, respectively. In a second PDX model harboring wild-type ESR1, vepdegestrant also demonstrated anti-tumor activity as a single agent as well as enhanced activity in combination with palbociclib. In this second model, both single agent vepdegestrant as well as vepdegestrant plus palbociclib treatment arms demonstrated superior anti-tumor activity relative to fulvestrant treatment alone or fulvestrant treatment plus palbociclib. 

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Our Clinical Trials

Overview

We, along with Pfizer, have several ongoing clinical trials of vepdegestrant, designed to potentially position vepdegestrant as a backbone ER-targeting therapy in breast cancer, including:

•VERITAC-2, a Phase 3 second/third-line clinical trial evaluating vepdegestrant as a monotherapy, in advanced/metast