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Study of Patritumab Deruxtecan Plus Pembrolizumab With Other Anticancer Agents in Participants With High-Risk Early-Stage Triple-Negative or Hormone Receptor-Low Positive/HER-2 Negative Breast Cancer (MK-1022-010, HERTHENA-Breast-03)

RecruitingPhase 2

An Open-label Randomized Phase 2 Study to Evaluate Safety and Efficacy of Patritumab Deruxtecan Plus Pembrolizumab Administered Either Before or After Carboplatin/Paclitaxel Plus Pembrolizumab Compared With Pembrolizumab in Combination With Chemotherapy Followed by Surgery and Adjuvant Pembrolizumab for High-Risk Early-Stage Triple-Negative or Hormone Receptor-Low Positive/Human Epidermal Growth Factor Receptor-2 Negative Breast Cancer (HERTHENA-Breast03)

Who can join

Ages 18 and older · All sexes

Full eligibility criteria
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

About the study

Researchers are looking for new ways to treat triple-negative breast cancer (TNBC) and hormone receptor (HR) low positive/human epidermal growth factor receptor-2 (HER2) negative breast cancer. The main goals of this study are to learn:

* About the safety of the study treatments and if people tolerate them * If people who receive patritumab deruxtecan, pembrolizumab, and chemotherapy before surgery have fewer cancer cells removed during surgery compared to those who receive only pembrolizumab (pembro) and chemotherapy.

What is being tested

Sponsor: Merck Sharp & Dohme LLC · Participants: 372 · Started: Mar 20, 2025

Contact the study team

Official record on ClinicalTrials.gov — NCT06797635

Locations in the U.S.

CaliforniaUCLA Hematology/Oncology - Parkside ( Site 0021), Santa Monica
IllinoisOrchard Healthcare Research Inc. ( Site 0006), Skokie
MontanaIntermountain Health St. Vincent Regional Hospital - Cancer Centers of Montana ( Site 0003), Billings
OregonNorthwest Cancer Specialists (Compass Oncology) ( Site 8003), Tigard
TennesseeSCRI Oncology Partners ( Site 7000), Nashville
TexasTexas Oncology - DFW ( Site 8000), Dallas
Houston Methodist Hospital ( Site 0022), Houston
VirginiaVirginia Oncology Associates (VOA) ( Site 8001), Norfolk

Conditions

From ClinicalTrials.gov, data retrieved Sep 30, 2026. Each study sets its own eligibility; the study team decides who can join.