Phase 1 IDE574 dual KAT6/KAT7 lysine acetyltransferase inhibitor ± fulvestrant (ER degrader)

This first-in-human, open-label, multicenter Phase 1 study evaluates IDE574 (oral small-molecule dual inhibitor of the epigenetic writer enzymes KAT6 and KAT7) from IDEAYA Biosciences, as monotherapy dose escalation (Part 1A) in selected locally advanced/metastatic solid tumors and as monotherapy expansion (Part 1B) in ER+, HER2- metastatic breast cancer. It also tests combination dose escalation (Part 2A) and expansion (Part 2B) of IDE574 plus fulvestrant, an estrogen receptor degrader marketed by AstraZeneca, in ER+, HER2- metastatic breast cancer that has progressed on prior therapy (2nd line+). The primary goals are safety/tolerability and defining dose(s), with pharmacokinetics/pharmacodynamics and preliminary antitumor activity as key secondary objectives. Scientifically, it probes whether dual KAT6/7 blockade can reset tumor lineage identity and drug tolerance programs in endocrine-resistant ER+ disease, including settings like ESR1-mutant tumors, where resistance to hormone-based therapy is common. Today’s care for ER+, HER2- metastatic breast cancer typically sequences endocrine therapy with CDK4/6 inhibitors, then targeted add-ons (e.g., PI3K/AKT/mTOR-pathway agents when biomarker-eligible) and later-line chemotherapy/antibody-drug conjugates; this trial explores an epigenetic mechanism to potentially extend endocrine sensitivity and deepen responses.