Arvinas and Pfizer Announce Positive Topline Results from Phase 3 VERITAC-2 Clinical Trial
– VERITAC-2 achieved its primary endpoint in the estrogen receptor 1-mutant population, demonstrating statistically significant and clinically meaningful improvement in progression-free survival –
– Vepdegestrant is the first PROTAC degrader to demonstrate clinical benefit in a Phase 3 trial –
Arvinas, Inc. (NASDAQ: ARVN) and Pfizer Inc. today revealed positive topline results from the Phase 3 VERITAC-2 clinical trial evaluating vepdegestrant monotherapy versus fulvestrant in adults with estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced or metastatic breast cancer whose disease progressed after prior treatments. This study is crucial as it's the first pivotal data for vepdegestrant, a potential first-in-class oral PROTAC ER degrader.
The trial successfully met its primary endpoint among patients with estrogen receptor 1 mutations, showing a significant improvement in progression-free survival compared to fulvestrant treatment. The results met the pre-specified hazard ratio target in this specific patient group. However, in the broader patient population assessed, the trial did not achieve statistical significance.
“The first Phase 3 data readout for a PROTAC degrader is groundbreaking,” stated John Houston, Ph.D., Chairperson and CEO at Arvinas. “These results indicate that vepdegestrant could offer significant benefits to patients with metastatic breast cancer, particularly for those with tumors that harbor estrogen receptor 1 mutations.”
At this time, overall survival data was still forthcoming, with less than a quarter of events required for analysis having occurred. Therefore, the ongoing trial continues to focus on overall survival as a critical secondary endpoint. Vepdegestrant demonstrated a favorable safety profile, consistent with findings from earlier studies. Comprehensive findings from the VERITAC-2 study will be showcased at a medical conference in the near future and submitted to regulatory authorities for potential approval.
“Advanced ER+/HER2- metastatic breast cancer presents many challenges for patients, particularly after treatment resistance develops,” shared Megan O’Meara, M.D., Pfizer's Interim Chief Development Officer of Oncology. “The findings from VERITAC-2 reinforce the promise of vepdegestrant as a potential treatment option that may provide patients with more time without disease progression.”
Designed to leverage the body's natural protein disposal mechanisms, vepdegestrant aims to specifically target and degrade estrogen receptors in patients with breast cancer. The U.S. Food and Drug Administration (FDA) has designated vepdegestrant as a Fast Track candidate for the treatment of adults with ER+/HER2- advanced or metastatic breast cancer previously treated with endocrine therapies.
Understanding Metastatic Breast Cancer
Worldwide, around 2.3 million new breast cancer cases were reported in 2022, with forecasts suggesting nearly 320,000 diagnoses in the U.S. by 2025. Approximately 70% of these cases involve estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+/HER2-) breast cancer, which significantly impacts treatment strategies. Notably, nearly 30% of women initially diagnosed with early-stage breast cancer will eventually experience metastatic breast cancer, the most advanced stage in which the disease spreads beyond the breast.
Though treatment advancements have improved patients' quality of life and overall survival, many still face resistance to current therapies. ESR1 mutations contribute to treatment resistance and are observed in about 40% of patients in the second-line setting, highlighting the need for innovative treatment options.
Details on the VERITAC-2 Clinical Trial
The Phase 3 VERITAC-2 study is a global, randomized investigation assessing the safety and efficacy of vepdegestrant (ARV-471) compared to fulvestrant in ER+/HER2- advanced breast cancer patients. This trial successfully enrolled 624 participants across 26 countries, all of whom had previously undergone treatment with a CDK4/6 inhibitor combined with endocrine therapy.
Patients were assigned to receive vepdegestrant daily or fulvestrant via intramuscular injection. The study's primary outcome was progression-free survival in both intent-to-treat and the ESR1 mutation populations as validated by independent central review, with overall survival being a key secondary goal.
Highlighting Vepdegestrant’s Role
Vepdegestrant stands out as an investigational, orally bioavailable PROTAC designed to degrade estrogen receptors specifically in ER+/HER2- breast cancer patients. Its development is pivotal for providing a novel therapeutic approach, ideally as both a monotherapy and in combination with other treatments, targeting the substantial unmet needs in this patient population.
In a collaboration formed in July 2021, Arvinas and Pfizer are jointly developing vepdegestrant, sharing associated costs and revenues. This strong partnership aims to push forward therapeutic innovations that could alter the treatment landscape for breast cancer significantly.
About Arvinas and Pfizer
Arvinas, based in New Haven, Connecticut, is a clinical-stage biotechnology firm directed towards enhancing treatments for patients dealing with severe diseases. The company's unique PROTAC platform focuses on developing therapies that effectively degrade disease-causing proteins. Along with vepdegestrant, Arvinas is advancing multiple investigational therapies targeting various conditions.
Pfizer is renowned for its commitment to advancing cancer therapies, utilizing an array of treatment mechanisms to target the disease effectively. The company strives to bring transformative therapies to patients with various cancers, including breast cancer, continuously enhancing their pipeline to meet patient needs.
Frequently Asked Questions
What is the significance of the VERITAC-2 trial results?
The VERITAC-2 trial demonstrated that vepdegestrant could significantly improve progression-free survival in patients with estrogen receptor 1 mutations, marking a milestone as the first PROTAC degrader to show clinical benefits.
What types of breast cancer does vepdegestrant target?
Vepdegestrant targets estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+/HER2-) breast cancer, specifically in cases that have progressed after prior treatments.
How does vepdegestrant work?
Vepdegestrant utilizes the body’s natural protein disposal system to selectively target and degrade estrogen receptors, potentially limiting the growth of breast cancer cells.
What is the next step for the VERITAC-2 trial results?
The detailed findings will be presented at an upcoming medical meeting and will be submitted to regulatory authorities to support potential approval.
What is the collaboration between Arvinas and Pfizer?
Arvinas and Pfizer joined forces to co-develop and co-commercialize vepdegestrant, sharing development costs and profits, aiming to broaden the treatment options for patients with breast cancer.
