The primary hypotheses are that sacituzumab tirumotecan as a single agent and sacituzumab tirumotecan plus pembrolizumab are superior to TPC with respect to progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) by blinded independent central review (BICR) in all participants.

Who can Participate

Inclusion Criteria: Has unresectable locally advanced or metastatic centrally-confirmed hormone receptor positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-) breast cancer Has radiographic disease progression on one or more lines of endocrine therapy for unresectable locally advanced/metastatic HR+/HER2- breast cancer, with one in combination with a CDK4/6 inhibitor Is a chemotherapy candidate Has an eastern cooperative oncology group (ECOG) performance status of 0 to 1 assessed within 7 days before randomization Has adequate organ function Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy Participants who are Hepatitis B surface antigen (HBsAg) positive are eligible if they have received HBV antiviral therapy for at least 4 weeks, and have undetectable HBV viral load Participants with a history of Hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable Exclusion Criteria: Has breast cancer amenable to treatment with curative intent Has experienced an early recurrence (<6 months after completing adjuvant/neoadjuvant chemotherapy) and therefore is eligible to receive second-line (2L) treatment Has symptomatic advanced/metastatic visceral spread at risk of rapidly evolving into life-threatening complications Has received prior chemotherapy for unresectable locally advanced or metastatic breast cancer Active autoimmune disease that has required systemic treatment in the past 2 years History of (noninfectious) pneumonitis/interstitial lung disease that requires steroids, or has current pneumonitis/interstitial lung disease Has an active infection requiring systemic therapy Detailed eligibility criteria is available on ClinicalTrials.gov. These requirements will be discussed with your doctor and/or study representative. ClinicalTrials.gov to learn more about this study.

Study ID

More information available at ClinicalTrials.gov: NCT06312176