This is a multicenter, open-label, Phase Ib/II randomized study designed to evaluate the safety, tolerability, dose-limiting toxicities (DLTs), and preliminary antitumor activity of JSKN016 in combination with the oral selective estrogen receptor degrader (SERD) D-0502 in patients with locally advanced or metastatic hormone receptor-positive (HR+), HER2-negative breast cancer who have previously progressed on CDK4/6 inhibitor-based endocrine therapy.
Approximately 60 patients will be randomized in a 1:1 ratio to receive JSKN016 administered intravenously every 2 weeks (Q2W) or every 3 weeks (Q3W), in combination with daily oral D-0502. Each dosing cohort will include a safety lead-in phase to assess DLTs prior to cohort expansion. Tumor response will be assessed according to RECIST v1.1.
Age ≥18 years
Histologically or cytologically confirmed locally advanced or metastatic HR-positive, HER2-negative breast cancer
HR-positive defined as ER and/or PR ≥1% by IHC
HER2-negative per ASCO/CAP guidelines
Active or untreated CNS metastases
Prior treatment with ADCs containing topoisomerase I inhibitor payloads
Active interstitial lung disease or pneumonitis
Uncontrolled cardiovascular disease or active infection