Arvinas, Inc., a biotechnology company in clinical development phases, together with Pfizer Inc., disclosed initial findings from the phase 1b segment of the TACTIVE-U study. This study explores the efficacy of the vepdegestrant and abemaciclib combination in patients with locally advanced or metastatic estrogen receptor-positive (ER+)/HER2-negative breast cancer. The data will be showcased as a poster at the 2024 San Antonio Breast Cancer Symposium (SABCS).
Results from 16 participants in the phase 1b study portion illustrated a manageable safety profile for the drug combination of 150 mg of abemaciclib administered twice daily with the vepdegestrant recommended phase 3 monotherapy dose (200 mg once daily). Participants exhibited a promising clinical benefit rate of 62.5%, including those with mutant and wild-type ESR1 cancers, all of whom had prior treatments involving a CDK4/6 inhibitor.
Pharmacokinetic analyses confirmed no significant drug interactions between vepdegestrant and abemaciclib, and abemaciclib’s exposure levels remained unaffected clinically. The study results also indicated that the safety profile aligned with the known characteristics of abemaciclib, as well as with previous vepdegestrant trial data. These positive results justify the advancement into the study’s phase 2, looking at the full dosage of abemaciclib (150 mg BID) partnered with vepdegestrant (200 mg QD) for advanced breast cancer post-CDK4/6 treatment.
Dr. Noah Berkowitz, M.D., Ph.D., Arvinas’s chief medical officer, stated, “The early outcomes from this phase 1b analysis in patients with cancer resistant to prior CDK4/6 inhibitors are encouraging. This evidence bolsters our belief in vepdegestrant’s potential in various combination therapies for metastatic breast cancer, aiming to become a leading backbone ER treatment. We are enthusiastic about progressing with phase 2 evaluations using standard abemaciclib doses with vepdegestrant.”
Roger Dansey, M.D., Pfizer’s chief development officer for oncology, added, “Our goal with vepdegestrant is to develop an innovative agent that could establish itself as a foundational endocrine therapy in ER+ metastatic breast cancer. We’re pleased to observe these preliminary results which support previously reported data, highlighting the potential of vepdegestrant combination therapy to fulfill unmet patient needs.”
The ongoing TACTIVE-U clinical trials, involving different combinations of vepdegestrant with abemaciclib, ribociclib, or samuraciclib, are being continuously monitored by Arvinas and Pfizer (ClinicalTrials.gov Identifiers: NCT05548127, NCT05573555, NCT06125522).
Vepdegestrant is an experimental oral PROTAC protein degrader, developed to target and degrade the estrogen receptor (ER) in patients with ER+/HER2- breast cancer. It’s being crafted for use as both a monotherapy and in combination therapies across varied settings of ER+/HER2- metastatic breast cancer.
In July 2021, Arvinas and Pfizer initiated a global partnership for the joint development and commercialization of vepdegestrant. Both companies will bear global development and commercialization expenses and share profits.
The U.S. Food and Drug Administration (FDA) has accorded Fast Track designation to vepdegestrant as a single therapy for adults with ER+/HER2- advanced or metastatic breast cancer previously exposed to endocrine-based treatments.
Arvinas, headquartered in New Haven, Connecticut, is dedicated to advancing patient outcomes in debilitating and life-threatening diseases through its innovative PROTAC protein degrader platform. The company is pursuing multiple investigational drugs, including vepdegestrant for ER+/HER2- breast cancer, ARV-393 targeting BCL6 for non-Hodgkin Lymphoma, and ARV-102 aimed at LRRK2 related neurodegenerative conditions.