Phase III Trial Data Show Vepdegestrant Produces Encouraging Outcomes in ER+/HER2- Advanced or Metastatic Breast Cancer

Image Credit: Adobe Stock Images/Tharindu

Results from the Phase III VERITAC-2 trial show that vepdegestrant (Arvinas, Pfizer) produced a statistically significant improvement in progression-free survival (PFS) compared to fulvestrant in patients with ER+/HER2- advanced or metastatic breast cancer who had previously progressed after treatment with CDK4/6 inhibitors and endocrine therapy. This marks the first major clinical data supporting vepdegestrant’s potential, according to Pfizer.¹

“The first Phase III data readout for a PROTAC degrader represents a significant achievement and these data show that vepdegestrant has the potential to provide clinically meaningful outcomes for thousands of patients with metastatic breast cancer whose tumors harbor estrogen receptor 1 mutations,” said John Houston, PhD, chairperson, CEO, president, Arvinas, in a press release. “We want to thank the patients and investigators who participated in this trial, and we look forward to sharing these data with health authorities as well as at a medical conference in 2025.”

The global, randomized VERITAC-2 trial assessed the efficacy and safety of vepdegestrant as a monotherapy in 624 patients who had previously been treated with a CDK4/6 inhibitor and endocrine therapy. Participants were randomly assigned to receive either vepdegestrant once daily for 28 days or fulvestrant, which was administered intramuscularly on day one and day 15 of the first cycle, then on day one of each subsequent 28-day cycle from the second cycle onward. The primary endpoint of the study was PFS in the intent-to-treat (ITT) and estrogen receptor 1-mutant populations, assessed via blinded independent central review, while key secondary endpoints included overall survival (OS).

The topline data revealed that vepdegestrant exceeded its pre-specified hazard ratio target of 0.60, although statistical significance was not reached in the ITT population. OS data were not mature enough at the time of the data readout. The safety profile of vepdegestrant was consistent with previous studies and no new signals were reported.¹

The American Cancer Society estimates that by the end of 2025, 316,950 women in the United States will be diagnosed with breast cancer, and 42,170 deaths. Breast cancer remains the most common cancer among women in the United States, accounting for 30% of all cancer diagnoses annually.

Current statistics show that women in the United States have a 13% lifetime risk of developing breast cancer, which is most common among middle-aged and older women, with a median diagnosis age of 62 years. Since 1989, the mortality rate has declined significantly, with a 44% reduction by 2022.²

According to Pfizer, 30% of women with breast cancer are expected to eventually develop metastatic disease, and that 70% of all breast cancer cases in the United States are ER+/HER2-.¹

“Patients with advanced ER+/HER2- metastatic breast cancer face significant clinical challenges, with limited treatment options following disease progression and the development of resistance to available endocrine therapies,” said Megan O’Meara, MD, interim chief development officer, Pfizer Oncology, in the press release. “These data from VERITAC-2 support the potential of vepdegestrant to give patients whose tumors harbor ESR1 mutations additional time without disease progression, compared to fulvestrant."

Arvinas and Pfizer plan to present full results from the study at an upcoming medical meeting and share the data with global regulatory authorities. Vepdegestrant was previously granted Fast Track designation by the FDA in 2024.¹

References

1. Arvinas and Pfizer Announce Positive Topline Results from Phase 3 VERITAC-2 Clinical Trial. Pfizer. March 11, 2025. Accessed March 12, 2025. https://www.pfizer.com/news/press-release/press-release-detail/arvinas-and-pfizer-announce-positive-topline-results-phase

2. Key Statistics for Breast Cancer. American Cancer Society. Accessed March 12, 2025. https://www.cancer.org/cancer/types/breast-cancer/about/how-common-is-breast-cancer.html