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)

NCT ID: NCT06797635

Last Updated: 2026-01-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

372 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-03-20

Study Completion Date

2034-12-31

Brief Summary

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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.

Detailed Description

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Conditions

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Breast Neoplasms Breast Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Part 1 is non-randomized. Part 2 is randomized 1:1:1.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Part 1, A: Pembrolizimab + patritumab deruxtecan → Pembrolizumab + paclitaxel + carboplatin

In Part 1, participants receive neoadjuvant pembrolizumab 200 mg via intravenous (IV) infusion every 3 weeks (Q3W) plus patritumab deruxtecan via IV infusion Q3W for 12 weeks, followed by pembrolizumab 200 mg via IV infusion Q3W plus paclitaxel 80 mg/m\^2 via IV infusion every week (QW) and carboplatin AUC1.5 mg/ml/min via IV infusion QW for 12 weeks. At 3 to 6 weeks after last dose of neoadjuvant treatment, participants will undergo surgery for their breast cancer.

Group Type EXPERIMENTAL

Patritumab deruxtecan

Intervention Type BIOLOGICAL

Administered via IV infusion as neoadjuvant treatment

Pembrolizumab

Intervention Type BIOLOGICAL

Administered via IV infusion as neoadjuvant treatment in Part 1 and via IV infusion as neoadjuvant and adjuvant treatment in Part 2

Paclitaxel

Intervention Type DRUG

Administered via IV infusion as neoadjuvant treatment

Carboplatin

Intervention Type DRUG

Administered via IV infusion as neoadjuvant treatment

Part 2, A: Pembrolizimab + patritumab deruxtecan → Pembrolizumab + paclitaxel + carboplatin

In Part 2, participants receive neoadjuvant pembrolizumab 200 mg IV infusion every Q3W plus patritumab deruxtecan (dose to be determined in part 1) IV infusion Q3W for 12 weeks, followed by pembrolizumab 200 mg IV infusion Q3W plus paclitaxel 80 mg/m\^2 IV infusion QW and carboplatin AUC1.5 mg/ml/min IV infusion QW for 12 weeks. At 3-6 weeks after last dose of neoadjuvant treatment, participants undergo surgery for breast cancer. After surgery, participants receive adjuvant pembrolizumab 400 mg IV every 6 weeks (Q6W) for \~30 weeks. Additional adjuvant treatment of physician's choice (TPC) may be given to participants with residual disease. TPC options are olaparib 300 mg oral twice daily (BID) for 1 year (participants with germline BRCA mutation \[gBRCAm\] only), capecitabine 1000-1250 mg/m\^2 oral BID days 1-14 and 22-35 Q6W for 4 six-week cycles or doxorubicin 60mg/m\^2 (or epirubicin 90 mg/m\^2) IV Q3W or every 2 weeks (Q2W) and cyclophosphamide 600 mg/m\^2 IV Q3W or Q2W for 4 doses.

Group Type EXPERIMENTAL

Patritumab deruxtecan

Intervention Type BIOLOGICAL

Administered via IV infusion as neoadjuvant treatment

Pembrolizumab

Intervention Type BIOLOGICAL

Administered via IV infusion as neoadjuvant treatment in Part 1 and via IV infusion as neoadjuvant and adjuvant treatment in Part 2

Paclitaxel

Intervention Type DRUG

Administered via IV infusion as neoadjuvant treatment

Carboplatin

Intervention Type DRUG

Administered via IV infusion as neoadjuvant treatment

Doxorubicin hydrochloride

Intervention Type DRUG

Administered via IV infusion as neoadjuvant treatment in Arm C and an option for adjuvant treatment for participants with residual disease in Arms A and B in Part 2

Epirubicin hydrochloride

Intervention Type DRUG

Administered via IV infusion as neoadjuvant treatment in Arm C and an option for adjuvant treatment for participants with residual disease in Arms A and B in Part 2

Cyclophosphamide

Intervention Type DRUG

Administered via IV infusion as neoadjuvant treatment in Arm C and an option for adjuvant treatment for participants with residual disease in Arms A and B in Part 2

Capecitabine

Intervention Type DRUG

Administered via oral tablets as an option for adjuvant treatment for participants with residual disease in Part 2

Olaparib

Intervention Type DRUG

Administered via oral tablets as an option for adjuvant treatment for participants with germline BRCA mutations and residual disease in Part 2

Part 2, B: Pembrolizumab + paclitaxel + carboplatin → Pembrolizumab + patritumab deruxtecan

In Part 2, participants receive neoadjuvant pembrolizumab 200 mg IV infusion Q3W plus paclitaxel 80 mg/m\^2 IV infusion QW and carboplatin AUC1.5 mg/ml/min IV infusion QW for 12 weeks, followed by pembrolizumab 200 mg IV infusion Q3W plus patritumab deruxtecan (dose to be determined in part 1) via IV infusion Q3W for 12 weeks. At 3 to 6 weeks after last dose of neoadjuvant treatment, participants will undergo surgery for their breast cancer. After surgery, participants will receive adjuvant pembrolizumab 400 mg IV infusion Q6W for \~30 weeks. Additional adjuvant TPC may be administered to participants with residual disease. TPC options include olaparib 300 mg oral BID for 1 year (participants with gBRCAm only), capecitabine 1000-1250 mg/m\^2 oral BID days 1-14 and 22-35 Q6W for 4 six-week cycles or doxorubicin 60mg/m\^2 (or epirubicin 90 mg/m\^2) IV infusion Q3W or Q2W and cyclophosphamide 600 mg/m\^2 IV infusion Q3W or Q2W for 4 doses.

Group Type EXPERIMENTAL

Patritumab deruxtecan

Intervention Type BIOLOGICAL

Administered via IV infusion as neoadjuvant treatment

Pembrolizumab

Intervention Type BIOLOGICAL

Administered via IV infusion as neoadjuvant treatment in Part 1 and via IV infusion as neoadjuvant and adjuvant treatment in Part 2

Paclitaxel

Intervention Type DRUG

Administered via IV infusion as neoadjuvant treatment

Carboplatin

Intervention Type DRUG

Administered via IV infusion as neoadjuvant treatment

Doxorubicin hydrochloride

Intervention Type DRUG

Administered via IV infusion as neoadjuvant treatment in Arm C and an option for adjuvant treatment for participants with residual disease in Arms A and B in Part 2

Epirubicin hydrochloride

Intervention Type DRUG

Administered via IV infusion as neoadjuvant treatment in Arm C and an option for adjuvant treatment for participants with residual disease in Arms A and B in Part 2

Cyclophosphamide

Intervention Type DRUG

Administered via IV infusion as neoadjuvant treatment in Arm C and an option for adjuvant treatment for participants with residual disease in Arms A and B in Part 2

Capecitabine

Intervention Type DRUG

Administered via oral tablets as an option for adjuvant treatment for participants with residual disease in Part 2

Olaparib

Intervention Type DRUG

Administered via oral tablets as an option for adjuvant treatment for participants with germline BRCA mutations and residual disease in Part 2

Part 2, C: Pembro + paclitaxel + carboplatin→ Pembro + doxorubicin (or epirubicin) +cyclophosphamide

In Part 2, participants receive neoadjuvant pembrolizumab 200 mg IV infusion Q3W plus paclitaxel 80 mg/m\^2 IV infusion QW and carboplatin AUC1.5 mg/ml/min via IV infusion QW for 12 weeks, followed by pembrolizumab 200 mg IV infusion Q3W plus doxorubicin 60mg/m\^2 (or epirubicin 90 mg/m\^2) IV infusion Q3W and cyclophosphamide 600 mg/m\^2 IV infusion Q3W for 12 weeks. At 3 to 6 weeks after last dose of neoadjuvant treatment, participants will undergo surgery for their breast cancer. After surgery, participants will receive adjuvant pembrolizumab 400 mg IV infusion Q6W for approximately 30 weeks. Additional adjuvant TPC may be administered to participants with residual disease. TPC options include olaparib 300 mg oral BID for 1 year (participants with gBRCAm only) or capecitabine 1000-1250 mg/m\^2 oral BID days 1-14 and 22-35 Q6W for 4 six-week cycles.

Group Type ACTIVE_COMPARATOR

Pembrolizumab

Intervention Type BIOLOGICAL

Administered via IV infusion as neoadjuvant treatment in Part 1 and via IV infusion as neoadjuvant and adjuvant treatment in Part 2

Paclitaxel

Intervention Type DRUG

Administered via IV infusion as neoadjuvant treatment

Carboplatin

Intervention Type DRUG

Administered via IV infusion as neoadjuvant treatment

Doxorubicin hydrochloride

Intervention Type DRUG

Administered via IV infusion as neoadjuvant treatment in Arm C and an option for adjuvant treatment for participants with residual disease in Arms A and B in Part 2

Epirubicin hydrochloride

Intervention Type DRUG

Administered via IV infusion as neoadjuvant treatment in Arm C and an option for adjuvant treatment for participants with residual disease in Arms A and B in Part 2

Cyclophosphamide

Intervention Type DRUG

Administered via IV infusion as neoadjuvant treatment in Arm C and an option for adjuvant treatment for participants with residual disease in Arms A and B in Part 2

Capecitabine

Intervention Type DRUG

Administered via oral tablets as an option for adjuvant treatment for participants with residual disease in Part 2

Olaparib

Intervention Type DRUG

Administered via oral tablets as an option for adjuvant treatment for participants with germline BRCA mutations and residual disease in Part 2

Interventions

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Patritumab deruxtecan

Administered via IV infusion as neoadjuvant treatment

Intervention Type BIOLOGICAL

Pembrolizumab

Administered via IV infusion as neoadjuvant treatment in Part 1 and via IV infusion as neoadjuvant and adjuvant treatment in Part 2

Intervention Type BIOLOGICAL

Paclitaxel

Administered via IV infusion as neoadjuvant treatment

Intervention Type DRUG

Carboplatin

Administered via IV infusion as neoadjuvant treatment

Intervention Type DRUG

Doxorubicin hydrochloride

Administered via IV infusion as neoadjuvant treatment in Arm C and an option for adjuvant treatment for participants with residual disease in Arms A and B in Part 2

Intervention Type DRUG

Epirubicin hydrochloride

Administered via IV infusion as neoadjuvant treatment in Arm C and an option for adjuvant treatment for participants with residual disease in Arms A and B in Part 2

Intervention Type DRUG

Cyclophosphamide

Administered via IV infusion as neoadjuvant treatment in Arm C and an option for adjuvant treatment for participants with residual disease in Arms A and B in Part 2

Intervention Type DRUG

Capecitabine

Administered via oral tablets as an option for adjuvant treatment for participants with residual disease in Part 2

Intervention Type DRUG

Olaparib

Administered via oral tablets as an option for adjuvant treatment for participants with germline BRCA mutations and residual disease in Part 2

Intervention Type DRUG

Other Intervention Names

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MK-1022 HER3-DXd U3-1402 MK-3475 KEYTRUDA® TAXOL® ONXAL® PARAPLATIN® ADRIAMYCIN® ELLENCE® CYTOXAN® XELODA® LYNPARZA®

Eligibility Criteria

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Inclusion Criteria

* 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

* Has uncontrolled or significant cardiovascular disease before randomization
* Has clinically significant corneal disease
* Has human immunodeficiency virus (HIV) infection with a history of Kaposi sarcoma and/or multicentric Castleman disease
* 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 a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease, or where suspected ILD/pneumonitis cannot be ruled out by standard diagnostic assessments
* Has an active infection requiring systemic therapy
* Has concurrent active HBV and HCV infection
* Has clinically severe respiratory compromise resulting from intercurrent pulmonary illness
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role lead

Daiichi Sankyo

INDUSTRY

Sponsor Role collaborator

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

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UCLA Hematology/Oncology - Parkside ( Site 0021)

Santa Monica, California, United States

Site Status RECRUITING

Orchard Healthcare Research Inc. ( Site 0006)

Skokie, Illinois, United States

Site Status RECRUITING

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

Billings, Montana, United States

Site Status RECRUITING

Northwest Cancer Specialists (Compass Oncology) ( Site 8003)

Tigard, Oregon, United States

Site Status RECRUITING

SCRI Oncology Partners ( Site 7000)

Nashville, Tennessee, United States

Site Status RECRUITING

Texas Oncology - DFW ( Site 8000)

Dallas, Texas, United States

Site Status RECRUITING

Houston Methodist Hospital ( Site 0022)

Houston, Texas, United States

Site Status RECRUITING

Virginia Oncology Associates (VOA) ( Site 8001)

Norfolk, Virginia, United States

Site Status RECRUITING

Seoul National University Hospital ( Site 2400)

Seoul, , South Korea

Site Status RECRUITING

Severance Hospital, Yonsei University Health System ( Site 2402)

Seoul, , South Korea

Site Status RECRUITING

Asan Medical Center ( Site 2401)

Seoul, , South Korea

Site Status RECRUITING

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

Badalona, Catalonia, Spain

Site Status RECRUITING

Clinica Universidad de Navarra ( Site 1703)

Madrid, Madrid, Comunidad de, Spain

Site Status RECRUITING

Hospital Universitario Reina Sofia ( Site 1702)

Córdoba, , Spain

Site Status RECRUITING

Taichung Veterans General Hospital ( Site 2502)

Taichung, , Taiwan

Site Status RECRUITING

National Cheng Kung University Hospital ( Site 2503)

Tainan, , Taiwan

Site Status RECRUITING

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

Taipei, , Taiwan

Site Status RECRUITING

Countries

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United States South Korea Spain Taiwan

Central Contacts

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Toll Free Number

Role: CONTACT

1-888-577-8839

Facility Contacts

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Study Coordinator

Role: primary

424-402-9520

Study Coordinator

Role: primary

888-577-8839

Study Coordinator

Role: primary

888-577-8839

Study Coordinator

Role: primary

888-577-8839

Study Coordinator

Role: primary

844-482-4812

Study Coordinator

Role: primary

214-370-1067

Study Coordinator

Role: primary

713-441-9948

Study Coordinator

Role: primary

844-482-4812

Study Coordinator

Role: primary

+82220720850

Study Coordinator

Role: primary

+82222288135

Study Coordinator

Role: primary

+82230103217

Study Coordinator

Role: primary

+34934978925

Study Coordinator

Role: primary

+34913531920

Study Coordinator

Role: primary

+34 957012408

Study Coordinator

Role: primary

+886423592525

Study Coordinator

Role: primary

+88662353535

Study Coordinator

Role: primary

886228970011x1686

Related Links

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http://www.merckclinicaltrials.com

Merck Clinical Trials Information

Other Identifiers

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MK-1022-010

Identifier Type: OTHER

Identifier Source: secondary_id

2024-514376-40-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

U1111-1307-7867

Identifier Type: REGISTRY

Identifier Source: secondary_id

1022-010

Identifier Type: -

Identifier Source: org_study_id

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