Arvinas, Inc. and Pfizer Inc. have released preliminary data from the phase 1b portion of the TACTIVE-U sub-study of vepdegestrant in combination with abemaciclib, for patients with locally advanced or metastatic estrogen receptor positive (ER+)/human epidermal growth factor receptor 2 negative (HER2-) breast cancer. The preliminary results from 16 patients in the phase 1b sub-study demonstrated a tolerable safety profile for the combination, with an encouraging clinical benefit rate of 62.5% observed among patients with both mutant esr1 and wild-type esr1 disease who had all been previously treated with a CDK4/6 inhibitor.
The key findings included in the poster presented at the 2024 San Antonio Breast Cancer Symposium (SABCS) on December 12, 2024, revealed that 100% of patients had prior treatment with a CDK4/6 inhibitor. The tolerability of the combination was generally consistent with the profile of abemaciclib and with results previously observed in other clinical trials of vepdegestrant. The most common any grade treatment-emergent adverse events (TEAE) were diarrhea, nausea, and fatigue. Encouraging preliminary antitumor activity was observed with a clinical benefit rate (CBR) of 62.5% in all CBR-eligible patients, and an objective response rate (ORR) in evaluable patients was 26.7% overall.
The recommended phase 2 dose was identified as 200 mg qd vepdegestrant and 150 mg bid abemaciclib. Additionally, there was no significant drug-drug interaction, and data reflected vepdegestrant has no clinically meaningful effect on abemaciclib exposure.
Arvinas and Pfizer are continuing to evaluate data from the ongoing TACTIVE-U clinical trial, which includes combinations of vepdegestrant plus abemaciclib, ribociclib, or samuraciclib.
Vepdegestrant is an investigational, orally bioavailable PROTAC protein degrader designed to specifically target and degrade the estrogen receptor (ER) for the treatment of patients with ER+/HER2 breast cancer. The U.S. Food and Drug Administration (FDA) has granted vepdegestrant fast track designation as a monotherapy in the treatment of adults with ER+/HER2 locally advanced or metastatic breast cancer previously treated with endocrine-based therapy.
Arvinas and Pfizer announced a global collaboration for the co-development and co-commercialization of vepdegestrant, with both companies sharing worldwide development costs, commercialization expenses, and profits.
Arvinas is a clinical-stage biotechnology company dedicated to improving the lives of patients suffering from debilitating and life-threatening diseases. Through its PROTAC protein degrader platform, the company is pioneering the development of protein degradation therapies designed to harness the body’s natural protein disposal system to selectively and efficiently degrade and remove disease-causing proteins. Arvinas is currently progressing multiple investigational drugs through clinical development programs, including vepdegestrant, arv-393, and arv-102. Following these announcements, the company's shares moved -1.6%, and are now trading at a price of $24.67. Check out the company's full 8-K submission here.