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NCT06797635PHASE2Recruiting

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)

Merck Sharp & Dohme LLC

Start Date

3/20/2025

Completion Date

12/31/2034

Summary

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.

Eligibility Criteria

Age Range: 18 years to No maximum

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

Interventions

BIOLOGICAL

Patritumab deruxtecan

BIOLOGICAL

Pembrolizumab

DRUG

Paclitaxel

DRUG

Carboplatin

DRUG

Doxorubicin hydrochloride

DRUG

Epirubicin hydrochloride

DRUG

Cyclophosphamide

DRUG

Capecitabine

DRUG

Olaparib

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Conditions

Breast NeoplasmsBreast Cancer

Locations

UCLA Hematology/Oncology - Parkside ( Site 0021)

Santa Monica, California 90404

United States

Orchard Healthcare Research Inc. ( Site 0006)

Skokie, Illinois 60077

United States

Intermountain Health St. Vincent Regional Hospital - Cancer Centers of Montana ( Site 0003)

Billings, Montana 59102

United States

Northwest Cancer Specialists (Compass Oncology) ( Site 8003)

Tigard, Oregon 97223

United States

SCRI Oncology Partners ( Site 7000)

Nashville, Tennessee 37203

United States

Texas Oncology - DFW ( Site 8000)

Dallas, Texas 75246

United States

Houston Methodist Hospital ( Site 0022)

Houston, Texas 77030

United States

Virginia Oncology Associates (VOA) ( Site 8001)

Norfolk, Virginia 23502

United States

Seoul National University Hospital ( Site 2400)

Seoul, 03080

South Korea

Severance Hospital, Yonsei University Health System ( Site 2402)

Seoul, 03722

South Korea

Asan Medical Center ( Site 2401)

Seoul, 05505

South Korea

Institut Català d'Oncologia (ICO) - Badalona ( Site 1700)

Badalona, Catalonia 08916

Spain

Clinica Universidad de Navarra ( Site 1703)

Madrid, Madrid, Comunidad de 28027

Spain

Hospital Universitario Reina Sofia ( Site 1702)

Córdoba, 14004

Spain

Taichung Veterans General Hospital ( Site 2502)

Taichung, 407

Taiwan

National Cheng Kung University Hospital ( Site 2503)

Tainan, 704

Taiwan

Koo Foundation Sun Yat-Sen Cancer Center ( Site 2501)

Taipei, 112

Taiwan