Patritumab Deruxtecan and Pembrolizumab for Breast Cancer

Inclusion Criteria: The main inclusion criteria include but are not limited to the following: * Has locally advanced, non-metastatic (M0), breast cancer, defined as any of the following combined primary tumor (T) and regional lymph node (N) staging per current American Joint Committee on Cancer (AJCC) criteria: cT1c, N1-N2; cT2, N0-N2; cT3, N0-N2; or cT4a-d, N0-N2 * Has centrally confirmed diagnosis of breast cancer that is triple-negative or HR-low+/HER2- breast cancer that will be treated according to the triple-negative breast cancer (TNBC) paradigm * Participants who are Hepatitis B surface antigen (HBsAg) positive are eligible if they have received Hepatitis B virus (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 * Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within 28 days prior to allocation/randomization * Has left ventricular ejection fraction (LVEF) of ≥50% or ≥ lower limit of normal (LLN) as assessed by echocardiogram (ECHO) or multigate acquisition scan (MUGA) scan Exclusion Criteria: The main exclusion criteria include but are not limited to the following: * Has uncontrolled or significant cardiovascular disease before randomization * Has any history of or evidence of any current leptomeningeal carcinomatosis. * Has clinically significant corneal disease * Has human immunodeficiency virus (HIV) infection with a history of Kaposi sarcoma and/or multicentric Castleman disease * Has evidence of ongoing, uncontrolled, systemic bacterial, fungal, or viral infection * Has received prior therapy with an anti-programmed death (PD)-1, anti-PD-L1, or anti-PD-L2 agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor * Has received any prior treatment, including radiation, systemic therapy, and/or definitive surgery for currently diagnosed breast cancer * Has received prior treatment with an anti-human epidermal growth factor receptor 3 (HER3) antibody and/or antibody-drug conjugate (ADC) that consists of an exatecan derivative that is a topoisomerase I inhibitor (e.g., trastuzumab deruxtecan) * Has metastatic (Stage IV) breast cancer or cN3 nodal involvement * Has known additional malignancy that is progressing or has required active treatment within the past 5 years * Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis * Has any history of interstitial lung disease (ILD)/pneumonitis irrespective of steroid use, or current or suspected ILD * Has an active infection requiring systemic therapy * Has concurrent active HBV and HCV infection * Has clinically severe respiratory compromise resulting from intercurrent pulmonary illness