FDA Fast Tracks Arvinas' and Pfizer’s Vepdegestrant for ER-Positive/HER2-Negative Breast Cancer

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The FDA has granted Fast Track designation to Arvinas’ and Pfizer’s vepdegestrant (ARV-471) monotherapy for adults with estrogen receptor (ER)–positive/human epidermal growth factor 2 (HER2)-negative locally advanced or metastatic breast cancer who received prior treatment with an endocrine-based therapy.¹

Data from the Phase I/II VERITAC trial (NCT04072952) showed promising findings for the novel oral PROteolysis Targeting Chimera (PROTAC) ER degrader in patients with ER-positive/HER2-negative breast cancer. Investigators are currently evaluating second-line vepdegestrant monotherapy in the ongoing Phase III VERITAC-2 trial as well as in combination with Ibrance (palbociclib) in the first-line setting for the ongoing lead-in cohort of the Phase III VERITAC-3 clinical trial. The drug is also being considered in combination with Verzenio (abemaciclib), Kisqali (ribociclib), samuraciclib, everolimus, and with the novel CDK4 inhibitor, PF-07220060.

“We are focused on the persisting unmet needs of people with ER-positive/HER2-negative breast cancer and doing all that we can to expedite the development of vepdegestrant as a novel, oral ER-targeted potential therapy for this patient community,” said John Houston, PhD, chairperson, CEO, and president of Arvinas, Inc., in a press release. “We are pleased the FDA has granted fast track designation for vepdegestrant, and we continue to believe this investigational drug has the potential to harness the body’s own natural protein disposal system to selectively and efficiently degrade and remove disease-causing proteins.”¹

Preclinical data show that vepdegestrant monotherapy produced ER degradation up to 97% in cancer cells across multiple ER-driven xenograft models. Vepdegestrant administration both with or without a CDK4/6 inhibitor was found to increase antitumor activity compared with standard Faslodex (fulvestrant).

Study investigators from the VERITAC-3 trial analyzed the safety and efficacy of vepdegestrant plus Ibrance in heavily pretreated patients with locally advanced or metastatic ER-positive/HER2-negative breast cancer.^2,3 Enrollment criteria included previous administration of at least one endocrine-based regimen and up to two chemotherapy regimens for advanced disease. Investigators identified 200 mg as the recommended Phase III dose of vepdegestrant.

The combination produced a clinical benefit rate (CBR) of 63% in all evaluable patients. Among 31 evaluable patients with measurable disease at baseline who were administered the combination, the objective response rate was 42%, whereas median progression-free survival was 11.1 months in all 46 patients enrolled in the trial.

In terms of safety, vepdegestrant plus Ibrance was found to have a manageable profile. The most common adverse events associated with either drug and occurring in at least 10% of the 46 total patients enrolled in the trial included neutropenia, fatigue, decreased platelet count, anemia, reduced white blood cell count, constipation, QT prolongation, diarrhea, nausea, hot flush, alopecia, arthralgia, decreased appetite, and vomiting.

“The receipt of Fast Track designation reinforces the potential of vepdegestrant to provide an important new therapeutic option for people with ER+/HER2- breast cancer whose disease has progressed,” said Roger Dansey, MD, chief development officer, Oncology, Pfizer, said in the release. “We are proud to continue our legacy of developing innovative treatment options for people impacted by metastatic breast cancer and look forward to working with the FDA as we advance our development program for vepdegestrant.”¹

References

1. Arvinas and Pfizer’s vepdegestrant (ARV-471) receives FDA fast track designation for the treatment of patients with ER+/HER2- metastatic breast cancer. News release. Arvinas, Inc. February 6, 2024. Accessed February 7, 2024. https://ir.arvinas.com/news-releases/news-release-details/arvinas-and-pfizers-vepdegestrant-arv-471-receives-fda-fast

2. Arvinas and Pfizer announce interim data from phase 1b trial of vepdegestrant in combination with palbociclib (Ibrance) and plans to expand vepdegestrant development program. News release. Arvinas, Inc. and Pfizer Inc. December 5, 2023. Accessed February 7, 2024. https://www.pfizer.com/news/press-release/press-release-detail/arvinas-and-pfizer-announce-interim-data-phase-1b-trial

3. Arvinas SABCS data presentation. Arvinas, Inc. December 6, 2023. Accessed February 7, 2024. https://edge.media-server.com/mmc/p/4s9bz59g/#Slides_6