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 factorreceptor 2 (HER2)- invasive breast carcinoma that is either locally advanced diseasenot amenable to resection with curative intent (herein called unresectable) ormetastatic disease not treatable with curative intent

• Has centrally-confirmed HR+ and HER2- results and human epidermal growth factorreceptor 3 (HER3) evaluable results from a biopsy obtained from a distant metastaticsite on or after the most recent line of therapy (with certain exceptions)

• Must have had progression or recurrence on prior cyclin-dependent kinase (CDK)4/6inhibitor + endocrine therapy (ET) with one of the following:

• Radiographic disease progression, as assessed by the investigator, on CDK4/6inhibitor + ET as 1L for treatment of unresectable locally advanced ormetastatic HR+/HER2- breast cancer. CDK4/6 inhibitor + ET must be the only lineof therapy received in the advanced setting, or

• Disease recurrence, either radiographic and/or confirmed histologically viabiopsy as assessed by the investigator, while on adjuvant ET in combinationwith a CDK4/6 inhibitor OR within 24 months from the date of last dose ofadjuvant CDK4/6 inhibitor

• Measurable disease per RECIST 1.1 as assessed by the local siteinvestigator/radiology

• Human immunodeficiency virus (HIV)-infected participants must have well controlledHIV on antiretroviral therapy (ART)

• An ECOG 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 settingas determined by the investigator

• Has a known germline breast cancer gene (BRCA) mutation (deleterious or suspecteddeleterious) where poly (ADP-ribose) polymerase (PARP) inhibitor(s) is a potentialtreatment option

• Has current visceral crisis or is at risk for impending visceral crisis that has ormay 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 metastaticbreast cancer (mBC)

• Has received prior treatment with an anti-HER3 antibody and/or antibody-drugconjugate (ADC) that consists of a topoisomerase I inhibitor (eg, T-DXd) or anyother 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) mayparticipate as long as at least 2 weeks have elapsed since the last dose oftherapy was administered

• Has received prior radiotherapy for non-CNS disease, or required corticosteroids forradiation-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 treatmentwithin the past 3 years

• History of (noninfectious) pneumonitis/interstitial lung disease (ILD) that requiredsteroids, has current pneumonitis/interstitial lung disease, or has suspectedILD/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 theirexcipients