Study of Patritumab Deruxtecan With Other Anticancer Agents in Participants With HER2 Positive Breast Cancer That Has Spread and Cannot Be Surgically Removed (MK-1022-009)

Researchers want to learn if patritumab deruxtecan (MK-1022) can treat certain breast cancers. The breast cancers being studied are HER2 positive unresectable locally advanced or metastatic (the cancer has spread to other parts of the body). The goals of this study are to learn:

* About the safety and how well people tolerate of patritumab deruxtecan
* How many people have the cancer respond (get smaller or go away) to treatment

The following countries will be participating in the trial: Canada, United Kingdom, Israel, Japan, South Korea, and USA.

Eligibility Criteria:
Inclusion Criteria:

The main inclusion criteria include but are not limited to the following:

* Has histologically confirmed HER2+ locally advanced unresectable breast cancer or metastatic breast cancer
* Human immunodeficiency virus (HIV)-infected participants must have well-controlled HIV on antiretroviral therapy (ART)
* 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 hepatitis B virus (HBV) viral load before allocation
* Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable
* Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 within 7 days before start of study intervention

Arm 1:

* Has received at least a minimum of 2 and a maximum of 5 prior lines of anti-HER2 therapy in the locally advanced or metastatic setting
* Had disease progression on or after any previous trastuzumab deruxtecan (T-DXd) treatment

Arm 2:

-Has received no more than 5 prior lines of anti-HER2 therapy in the locally advanced or metastatic setting

Arm 3:

-Has received and had disease progression from T-DXd treatment in any setting and a maximum of 3 prior lines of anti-HER2 therapy in the locally advanced or metastatic setting. T-DXd must be the most recent therapy received before enrollment.

Exclusion Criteria:

The main exclusion criteria include but are not limited to the following:

* Uncontrolled or significant cardiovascular disease
* History of (noninfectious) pneumonitis/interstitial lung disease (ILD) that required steroids or has current pneumonitis/interstitial lung disease
* Has clinically severe respiratory compromise
* Has any history of or evidence of any current leptomeningeal disease
* Has clinically significant corneal disease
* Evidence of ongoing uncontrolled systemic bacterial, fungal, or viral infection
* HIV infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
* Known additional malignancy that is progressing or has required active treatment within the past 3 years
* Evidence of spinal cord compression or brain metastases
* Has an active infection requiring systemic therapy
* Concurrent active HBV and HCV infection
* Has had major surgical procedure (excluding placement of vascular access) less than 28 days

Arm 3 ONLY

- Has received prior treatment with tucatinib, lapatinib, or neratinib, or any investigational HER2-targeted tyrosine kinase inhibitors in the locally advanced or metastatic setting