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

Eligibility Criteria

• * 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 on or after the most recent line of therapy (with certain exceptions)
• * 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
• * 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 (ART)
• * An ECOG performance status of 0 or 1 assessed within 7 days before randomization
• * 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 (mBC)
• * Has received prior treatment with an anti-HER3 antibody and/or antibody-drug conjugate (ADC) 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
• * Note: 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-CNS disease, or required corticosteroids for radiation-related toxicities, within 14 days of the first dose of study intervention
• * Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
• * Known additional malignancy that is progressing or has required active treatment within the past 3 years
• * History of (noninfectious) pneumonitis/interstitial lung disease (ILD) that required steroids, has current pneumonitis/interstitial lung disease, or has suspected ILD/pneumonitis that cannot be ruled out by imaging at Screening
• * Severe hypersensitivity (≥Grade 3) to HER3-DXd and/or any of its excipients
• * Severe hypersensitivity (≥Grade 3) to all the available TPC and/or any of their excipients