A Clinical Study of Patritumab Deruxtecan to Treat Breast Cancer (MK-1022-016)

Inclusion Criteria: The main inclusion criteria include but are not limited to the following: * Has a diagnosis of hormone receptor positive (HR+)/human epidermal growth factor receptor 2 (HER2)- invasive breast carcinoma that is either locally advanced disease not amenable to resection with curative intent (herein called unresectable) or metastatic disease not treatable with curative intent * Has centrally-confirmed HR+ and HER2- results and human epidermal growth factor receptor 3 (HER3) evaluable results from a biopsy obtained from a distant metastatic site or a locally advanced lesion on or after the time of diagnosis of locally advanced unresectable or metastatic breast cancer. A new biopsy obtained after progression of the most recent line of therapy is preferred * Must have had progression or recurrence on prior cyclin-dependent kinase (CDK)4/6 inhibitor + endocrine therapy (ET) with one of the following: * Radiographic disease progression, as assessed by the investigator, on CDK4/6 inhibitor + ET as 1L for treatment of unresectable locally advanced or metastatic HR+/HER2- breast cancer. CDK4/6 inhibitor + ET must be the only line of therapy received in the advanced setting, or * Disease recurrence, either radiographic and/or confirmed histologically via biopsy as assessed by the investigator, while on adjuvant ET in combination with a CDK4/6 inhibitor OR within 24 months from the date of last dose of adjuvant CDK4/6 inhibitor * Has measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology * Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy * Has an Eastern Cooperative Oncology Group performance status of 0 or 1 assessed within 7 days before randomization Exclusion Criteria: The main exclusion criteria include but are not limited to the following: * Has breast cancer amenable to treatment with curative intent * Is eligible to receive additional endocrine-based treatment in the advanced setting as determined by the investigator * Has a known germline breast cancer gene (BRCA) mutation (deleterious or suspected deleterious) where poly (ADP-ribose) polymerase (PARP) inhibitor(s) is a potential treatment option * Has current visceral crisis or is at risk for impending visceral crisis that has or may cause imminent organ compromise and/or other life-threatening complications * Has any of the following: a pulse oximeter reading \<92% at rest, or requires intermittent supplemental oxygen, or requires chronic supplemental oxygen * Has uncontrolled, significant cardiovascular disease or cerebrovascular disease * Has ≥Grade 2 peripheral neuropathy. * Has clinically significant corneal disease * Has received prior chemotherapy for unresectable locally advanced or metastatic breast cancer * Has received prior treatment with an anti-HER3 antibody and/or antibody-drug conjugate that consists of a topoisomerase I inhibitor (eg, T-DXd) or any other topoisomerase I inhibitor therapy * Has received prior systemic anticancer therapy within 4 weeks (or 5 half-lives, whichever is shorter) before randomization; participants previously treated with ET plus a CDK4/6 inhibitor may participate as long as at least 2 weeks have elapsed since the last dose of therapy was administered * Has received prior radiotherapy for non-central nervous system disease, or required corticosteroids for radiation-related toxicities, within 14 days of the first dose of study intervention * Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy * Has known additional malignancy that is progressing or has required active treatment within the past 3 years * Has history of (noninfectious) interstitial lung disease (ILD) or pneumonitis irrespective of steroid use, or has current ILD or suspected ILD, or ILD that cannot be ruled out by imaging at Screening * Has severe hypersensitivity (≥Grade 3) to HER3-DXd and/or any of its excipients * Has severe hypersensitivity (≥Grade 3) to all the available TPC and/or any of their excipients