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RecruitingInterventionalPhase 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)

NCT ID: NCT06797635Sponsor: Merck Sharp & Dohme LLCLast updated: 2026-05-20

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.

Arms & interventions

  • BiologicalPatritumab deruxtecan

    Administered via IV infusion as neoadjuvant treatment

  • BiologicalPembrolizumab

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

  • DrugPaclitaxel

    Administered via IV infusion as neoadjuvant treatment

  • DrugCarboplatin

    Administered via IV infusion as neoadjuvant treatment

  • DrugDoxorubicin 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

  • DrugEpirubicin 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

  • DrugCyclophosphamide

    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

  • DrugCapecitabine

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

  • DrugOlaparib

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

Outcome measures

Primary

  • Part 1: Number of Participants Experiencing an Adverse Event (AE)

    An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. The number of participants who experience an AE will be presented for Part 1.

    Time frame: Up to ~43 weeks

  • Part 1: Number of Participants Who Experience One or More Dose-Limiting Toxicities (DLTs)

    A DLT is defined by the National Cancer Institute Common Terminology for Adverse Events (NCI CTCAE) Version 5.0, assessed by investigator as drug-related: Grade (gr) 3 or 4 nonhematologic toxicity (with exceptions); gr 3 or gr 4 laboratory values (with exceptions); gr 3 or 4 febrile neutropenia; prolonged delay (\>2 weeks) in initiating Cycle 2 (cycle length = 3 weeks) due to intervention-related toxicity; any intervention-related toxicity that causes the participant to discontinue intervention during Cycle 1; interstitial lung disease as per investigator; any other gr ≥3 pulmonary toxicity; or gr 5 toxicity.

    Time frame: Up to 21 days

  • Part 1: Number of Participants who Discontinued Study Treatment Due to an AE

    An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. The number of participants who discontinued study treatment due to an AE will be presented for Part 1.

    Time frame: Up to ~30 weeks

  • Part 2: Pathological Complete Response (pCR) Rate Using the Definition of ypT0/Tis ypN0

    pCR (ypT0/Tis ypN0) is defined as the absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes after completion of neoadjuvant systemic therapy at the time of definitive surgery.

    Time frame: Up to ~30 weeks

  • Part 2: Number of Participants Experiencing an AE

    An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. The number of participants who experience an AE will be presented for Part 2.

    Time frame: Up to ~103 weeks

  • Part 2: Number of Participants who Discontinued Study Treatment Due to an AE

    An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. The number of participants who discontinued study treatment due to an AE will be presented for Part 2.

    Time frame: Up to ~90 weeks

Secondary

  • Part 2: pCR-No Ductal Carcinoma in Situ (DCIS) Rate Using the Definition of ypT0 ypN0

    Time frame: Up to ~30 weeks

  • Part 2: Event-Free Survival (EFS)

    Time frame: Up to ~100 months

  • Part 2: Overall Survival (OS)

    Time frame: Up to ~100 months

  • Part 2: Distant Progression or Distant Recurrence-Free Survival (DPDRFS)

    Time frame: Up to ~100 months

  • Part 2: Residual Cancer Burden (RCB)

    Time frame: Up to ~30 weeks

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No
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

Study locations (8)

UCLA Hematology/Oncology - Parkside ( Site 0021)

Santa Monica, California, 90404

Recruiting
Study Coordinator · Contact

Orchard Healthcare Research Inc. ( Site 0006)

Skokie, Illinois, 60077

Recruiting
Study Coordinator · Contact

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

Billings, Montana, 59102

Recruiting
Study Coordinator · Contact

Northwest Cancer Specialists (Compass Oncology) ( Site 8003)

Tigard, Oregon, 97223

Recruiting
Study Coordinator · Contact

SCRI Oncology Partners ( Site 7000)

Nashville, Tennessee, 37203

Recruiting
Study Coordinator · Contact

Texas Oncology - DFW ( Site 8000)

Dallas, Texas, 75246

Recruiting
Study Coordinator · Contact

Houston Methodist Hospital ( Site 0022)

Houston, Texas, 77030

Recruiting
Study Coordinator · Contact

Virginia Oncology Associates (VOA) ( Site 8001)

Norfolk, Virginia, 23502

Recruiting
Study Coordinator · Contact