Arvinas and Pfizer Report Positive Phase 3 VERITAC-2 Trial Results

Arvinas Inc. and Pfizer Inc. have announced promising results from the Phase 3 VERITAC-2 clinical trial, which evaluated vepdegestrant as a monotherapy against fulvestrant for patients with estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+/HER2-) advanced or metastatic breast cancer. This trial focused on patients who previously received treatment with cyclin-dependent kinase (CDK) 4/6 inhibitors and endocrine therapy.

Significantly, the trial's primary endpoint was met in the estrogen receptor 1-mutant (ESR1m) population, indicating a statistically noteworthy and meaningful improvement in progression-free survival (PFS) compared to fulvestrant. The trial surpassed the anticipated target hazard ratio of 0.60 within this group. However, it did not show statistical significance for PFS improvement in the overall intent-to-treat (ITT) population.

Dr. John Houston, the Chairperson, CEO, and President of Arvinas, described the Phase 3 data as a notable achievement. He stressed the potential of vepdegestrant to deliver significant outcomes for patients with metastatic breast cancer characterized by estrogen receptor 1 mutations. He also expressed gratitude to the patients and researchers involved in the trial and conveyed plans to present the data to health authorities and at a medical conference in 2025.

At the time of analysis, overall survival data was still immature, with less than 25% of the necessary events having occurred. The trial continues to evaluate overall survival as a crucial secondary measure. Vepdegestrant was generally well-tolerated, showing a safety profile in line with prior studies. Comprehensive results from VERITAC-2 will soon be presented at a medical conference and reviewed by global regulatory authorities for potential regulatory submissions.

Dr. Megan O’Meara, Interim Chief Development Officer at Pfizer Oncology, emphasized the clinical hurdles faced by patients with advanced ER+/HER2- metastatic breast cancer, noting limited treatment options post-disease progression and resistance development. She stated that the findings from VERITAC-2 highlight the potential of vepdegestrant to offer these patients extended periods without disease progression compared to fulvestrant.

Vepdegestrant is an oral investigational PROTAC ER degrader developed jointly by Arvinas and Pfizer. It targets the estrogen receptor, leveraging the body’s protein disposal system to degrade it. In February 2024, the U.S. Food and Drug Administration (FDA) granted Fast Track designation for vepdegestrant’s investigation in adults with ER+/HER2- advanced or metastatic breast cancer previously treated with endocrine-based therapy.

Approximately 2.3 million new breast cancer cases were reported worldwide in 2022, with an estimated 320,000 diagnoses expected in the U.S. by 2025. ER+/HER2- breast cancer constitutes about 70% of all breast cancer cases. Nearly 30% of patients diagnosed with early-stage breast cancer eventually develop metastatic breast cancer (MBC), the disease's most advanced stage. Despite treatment advances, most MBC patients eventually develop resistance to standard treatments. ESR1 mutations are a frequent cause of such resistance, found in about 40% of second-line patients.

The Phase 3 VERITAC-2 trial is an international randomized study assessing the efficacy and safety of vepdegestrant compared to fulvestrant in individuals with ER+/HER2- advanced or metastatic breast cancer. The trial included 624 participants from 26 countries, all of whom had undergone previous treatment with a CDK4/6 inhibitor and endocrine therapy. Participants received either daily oral vepdegestrant or intramuscular fulvestrant on a specified schedule. The primary endpoint was PFS in the intent-to-treat and ESR1m populations as reviewed independently. Overall survival serves as a key secondary endpoint.

Vepdegestrant represents an innovative approach as a PROTAC protein degrader, aiming to precisely target and eliminate the estrogen receptor in ER+/HER2- breast cancer patients. Arvinas and Pfizer announced a collaboration in July 2021 for the global development and commercialization of vepdegestrant, sharing costs, expenses, and profits. The FDA has recognized vepdegestrant with Fast Track designation for its potential as a monotherapy in treating advanced ER+/HER2- breast cancer previously treated with endocrine-based therapy.