Arvinas Advances Vepdegestrant into Phase 3 Trials for Breast Cancer and Updates Pipeline Milestones
Key Insights
Arvinas plans to initiate two Phase 3 trials in 2025 for vepdegestrant in ER+/HER2- metastatic breast cancer (search), one in the first-line setting with atirmociclib and another in the second-line setting with a CDK4/6 (search) inhibitor.
Topline data from the Phase 3 VERITAC-2 monotherapy trial of vepdegestrant in second-line-plus ER+/HER2- metastatic breast cancer (search) is anticipated in the first quarter of 2025.
Arvinas is set to present initial data from the Phase 1 trial of ARV-393 in B-cell lymphomas (search) and file an IND application for a novel PROTAC KRAS G12D (search) degrader in 2025.
Arvinas, Inc. (Nasdaq: ARVN) has announced updated guidance for its clinical trials, highlighting the advancement of vepdegestrant, a PROTAC ER degrader, into Phase 3 studies for estrogen receptor (search)-positive/human epidermal growth factor receptor 2-negative (ER+/HER2-) breast cancer (search). The company, in collaboration with Pfizer, is planning to initiate two Phase 3 combination trials in 2025, marking a significant step forward in addressing this prevalent cancer subtype. These trials aim to improve outcomes for patients with locally advanced or metastatic disease.
Vepdegestrant Combination Trials in Breast Cancer
Arvinas will combine vepdegestrant with Pfizer’s novel investigational CDK4 (search) inhibitor, atirmociclib, in a first-line Phase 3 trial. A second Phase 3 trial will evaluate vepdegestrant in combination with a CDK4/6 (search) inhibitor in the second-line setting. The prioritization of the vepdegestrant plus atirmociclib combination has led to the VERITAC-3 trial, which was evaluating vepdegestrant plus palbociclib in the first-line setting, not proceeding beyond the study lead-in.
Topline data from the Phase 3 VERITAC-2 monotherapy trial of vepdegestrant in patients with second-line-plus ER+/HER2- metastatic breast cancer (search) is anticipated in the first quarter of 2025. This trial is designed to assess the efficacy and safety of vepdegestrant as a single agent in patients who have progressed on prior endocrine therapies.
Expanding Pipeline: ARV-102, ARV-393, and KRAS G12D Degrader
Beyond breast cancer (search), Arvinas is also advancing its pipeline with programs targeting neurodegenerative disorders and B-cell lymphomas (search). A Phase 1 trial with PROTAC LRRK2 degrader ARV-102 has been initiated in patients with Parkinson’s disease (search). Initial data from this trial, along with single-ascending dose data from the trial in healthy volunteers, are expected to be presented in the first half of 2025. These data are anticipated to highlight the potential of PROTAC degraders in addressing neurodegenerative diseases.
Furthermore, Arvinas plans to present initial data from the ongoing Phase 1 trial of ARV-393, a PROTAC BCL6 degrader, in patients with B-cell lymphomas (search). The company also intends to file an Investigational New Drug (IND) application for a novel PROTAC KRAS G12D (search) degrader, expanding its reach into additional cancer targets.
Leadership Transition
Arvinas announced the appointment of Alex Santini, Senior Vice President, Global and U.S. Market Access, as interim Chief Commercial Officer, effective January 17, 2025. This transition follows the departure of John Northcott, Chief Commercial Officer, for personal reasons. Dr. John Houston, Chairperson, Chief Executive Officer and President at Arvinas, expressed confidence in Mr. Santini's ability to lead the commercial organization as the company prepares for potential product launches.
About Vepdegestrant
Vepdegestrant is an investigational, orally bioavailable PROTAC protein degrader specifically designed to target and degrade the estrogen receptor (search) (ER) in ER+/HER2- breast cancer (search). It is being developed as both a monotherapy and in combination with other agents across multiple treatment settings. The U.S. Food and Drug Administration (FDA) has granted Vepdegestrant Fast Track designation as a monotherapy for adults with ER+/HER2- locally advanced or metastatic breast cancer previously treated with endocrine-based therapy.
Arvinas is pioneering the development of protein degradation therapies through its PROTAC platform, harnessing the body’s natural protein disposal system to selectively remove disease-causing proteins. The company's pipeline includes multiple investigational drugs targeting various diseases, including breast cancer (search), lymphoma, and neurodegenerative disorders.