PS5-09-30: A phase 1/2 trial evaluating the safety, tolerability, and efficacy of the KAT6 inhibitor, PF-07248144, in combination with vepdegestrant in patients with ER+/HER2− locally advanced or metastatic breast cancer
Abstract
Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in combination with endocrine therapy are standard for the first-line (1L) treatment of estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER+/HER2−) advanced/metastatic breast cancer (ABC). Although CDK4/6 inhibitors significantly prolong progression-free survival (PFS) in patients with ER+/HER2− ABC, resistance ultimately occurs. For patients who develop resistance to CDK4/6i-based therapy, there is no universal standard of care, highlighting a key unmet need for this patient population. PF-07248144 is a novel, oral, selective inhibitor of KAT6A and KAT6B, two histone lysine acetyltransferases that regulate lineage-specific gene transcription via H3K23 acetylation. Vepdegestrant (ARV-471/PF-07850327) is an oral PROteolysis TArgeting Chimera (PROTAC) ER degrader that has exhibited clinical activity as monotherapy in heavily pretreated patients with ER+/HER2− ABC. Here, we describe a phase 1/2 study that aims to evaluate the safety, tolerability, and efficacy of the KAT6 inhibitor, PF-07248144, in combination with vepdegestrant in patients with ER+/HER2− ABC (NCT04606446).
This is an open-label, multicenter, phase 1/2 study of PF-07248144 as monotherapy or in combination for patients with advanced or metastatic solid tumors, including breast cancer. The study is comprised of two parts: dose escalation (Part 1) and dose expansion (Part 2). Parts 1E and 2E are focused herein and are evaluating…
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