SABCS 2022: Update From First-in-Human Trial of ARV-471 in Advanced Breast Cancer

By: Vanessa A. Carter, BS
Posted: Wednesday, December 14, 2022

Sara Hurvitz, MD, FACP, of the University of California, Los Angeles, and colleagues evaluated the efficacy of two doses of ARV-471—a selective, orally administered proteolysis targeting chimera protein degrader—in patients with estrogen receptor–positive, HER2-negative, locally advanced or metastatic breast cancer. The results of the phase II dose-expansion VERITAC study were presented during the 2022 San Antonio Breast Cancer Symposium (SABCS; Abstract GS3-03).

“ARV-471 monotherapy showed evidence of clinical activity based on clinical benefit rate, which was further enhanced in the subgroup with ESR1 mutations,” concluded the investigators. “The manageable adverse event profile observed in the phase I portion of the study was maintained during cohort expansion at doses of 200 mg daily and 500 mg daily.”

The study authors focused on 71 patients with estrogen receptor–positive, HER2-negative, locally advanced or metastatic breast cancer who received more than one prior endocrine therapy, a CDK4/6 inhibitor, and chemotherapy. Participants were administered ARV-471 monotherapy at 200 mg (n = 35) or 500 mg (n = 36) daily.

The median patient age was 60. The median number of prior regimens in all settings was four; all patients received prior CDK4/6 inhibitors, 78.9% had been given prior fulvestrant, and 73.2% had received prior chemotherapy.

Overall, ARV-471 was reported to be well tolerated at both doses, with the most common treatment-related adverse events being nausea and fatigue. ARV-471 treatment was discontinued in two patients on 500 mg and one patient on 200 mg because of treatment-emergent adverse events. Additionally, three patients on 500 mg required dose reductions as a result of these events. Individuals receiving treatment at 500 mg demonstrated a higher clinical benefit rate than those treated at 200 mg (38.9% vs. 37.1%). Among participants with mutant ESR1, clinical benefit rates for the 500-mg and 200-mg cohorts were 54.5% and 47.4%, respectively.

Disclosure: For full disclosures of the study authors, visit sabcs.org.

2022 San Antonio Breast Cancer Symposium

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