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)

NCT06797635 | Recruiting Phase 2 FDA Drug

• 4 other identifiers: 1022-010MK-1022-0102024-514376-40-00U1111-1307-7867
• Study Type: interventional
• Target: 372
• Locations: 4 countries
• Sites: 17

Brief 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.

Conditions

Breast Neoplasms; Breast Cancer

Outcome Measures

Primary Outcomes (6)

• 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.

  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.

  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.

  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.

  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.

  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.

  Up to ~90 weeks

Secondary Outcomes (5)

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

  Up to ~30 weeks

• Part 2: Event-Free Survival (EFS)

  Up to ~100 months

• Part 2: Overall Survival (OS)

  Up to ~100 months

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

  Up to ~100 months

• Part 2: Residual Cancer Burden (RCB)

  Up to ~30 weeks

Study Arms (4)

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

EXPERIMENTAL

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.

Biological: Patritumab deruxtecan; Biological: Pembrolizumab; Drug: Paclitaxel; Drug: Carboplatin

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

EXPERIMENTAL

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.

Biological: Patritumab deruxtecan; Biological: Pembrolizumab; Drug: Paclitaxel; Drug: Carboplatin; Drug: Doxorubicin hydrochloride; Drug: Epirubicin hydrochloride; Drug: Cyclophosphamide; Drug: Capecitabine; Drug: Olaparib

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

EXPERIMENTAL

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.

Biological: Patritumab deruxtecan; Biological: Pembrolizumab; Drug: Paclitaxel; Drug: Carboplatin; Drug: Doxorubicin hydrochloride; Drug: Epirubicin hydrochloride; Drug: Cyclophosphamide; Drug: Capecitabine; Drug: Olaparib

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

ACTIVE COMPARATOR

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.

Biological: Pembrolizumab; Drug: Paclitaxel; Drug: Carboplatin; Drug: Doxorubicin hydrochloride; Drug: Epirubicin hydrochloride; Drug: Cyclophosphamide; Drug: Capecitabine; Drug: Olaparib

Interventions

Patritumab deruxtecan BIOLOGICAL

Administered via IV infusion as neoadjuvant treatment

Also known as: MK-1022, HER3-DXd, U3-1402

Part 1, A: Pembrolizimab + patritumab deruxtecan → Pembrolizumab + paclitaxel + carboplatin; Part 2, A: Pembrolizimab + patritumab deruxtecan → Pembrolizumab + paclitaxel + carboplatin; Part 2, B: Pembrolizumab + paclitaxel + carboplatin → Pembrolizumab + patritumab deruxtecan

Pembrolizumab BIOLOGICAL

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

Also known as: MK-3475, KEYTRUDA®

Part 1, A: Pembrolizimab + patritumab deruxtecan → Pembrolizumab + paclitaxel + carboplatin; Part 2, A: Pembrolizimab + patritumab deruxtecan → Pembrolizumab + paclitaxel + carboplatin; Part 2, B: Pembrolizumab + paclitaxel + carboplatin → Pembrolizumab + patritumab deruxtecan; Part 2, C: Pembro + paclitaxel + carboplatin→ Pembro + doxorubicin (or epirubicin) +cyclophosphamide

Epirubicin hydrochloride 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

Also known as: ELLENCE®

Part 2, A: Pembrolizimab + patritumab deruxtecan → Pembrolizumab + paclitaxel + carboplatin; Part 2, B: Pembrolizumab + paclitaxel + carboplatin → Pembrolizumab + patritumab deruxtecan; Part 2, C: Pembro + paclitaxel + carboplatin→ Pembro + doxorubicin (or epirubicin) +cyclophosphamide

Cyclophosphamide 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

Also known as: CYTOXAN®

Part 2, A: Pembrolizimab + patritumab deruxtecan → Pembrolizumab + paclitaxel + carboplatin; Part 2, B: Pembrolizumab + paclitaxel + carboplatin → Pembrolizumab + patritumab deruxtecan; Part 2, C: Pembro + paclitaxel + carboplatin→ Pembro + doxorubicin (or epirubicin) +cyclophosphamide

Capecitabine DRUG

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

Also known as: XELODA®

Part 2, A: Pembrolizimab + patritumab deruxtecan → Pembrolizumab + paclitaxel + carboplatin; Part 2, B: Pembrolizumab + paclitaxel + carboplatin → Pembrolizumab + patritumab deruxtecan; Part 2, C: Pembro + paclitaxel + carboplatin→ Pembro + doxorubicin (or epirubicin) +cyclophosphamide

Olaparib DRUG

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

Also known as: LYNPARZA®

Part 2, A: Pembrolizimab + patritumab deruxtecan → Pembrolizumab + paclitaxel + carboplatin; Part 2, B: Pembrolizumab + paclitaxel + carboplatin → Pembrolizumab + patritumab deruxtecan; Part 2, C: Pembro + paclitaxel + carboplatin→ Pembro + doxorubicin (or epirubicin) +cyclophosphamide

Paclitaxel DRUG

Administered via IV infusion as neoadjuvant treatment

Also known as: TAXOL®, ONXAL®

Part 1, A: Pembrolizimab + patritumab deruxtecan → Pembrolizumab + paclitaxel + carboplatin; Part 2, A: Pembrolizimab + patritumab deruxtecan → Pembrolizumab + paclitaxel + carboplatin; Part 2, B: Pembrolizumab + paclitaxel + carboplatin → Pembrolizumab + patritumab deruxtecan; Part 2, C: Pembro + paclitaxel + carboplatin→ Pembro + doxorubicin (or epirubicin) +cyclophosphamide

Carboplatin DRUG

Administered via IV infusion as neoadjuvant treatment

Also known as: PARAPLATIN®

Part 1, A: Pembrolizimab + patritumab deruxtecan → Pembrolizumab + paclitaxel + carboplatin; Part 2, A: Pembrolizimab + patritumab deruxtecan → Pembrolizumab + paclitaxel + carboplatin; Part 2, B: Pembrolizumab + paclitaxel + carboplatin → Pembrolizumab + patritumab deruxtecan; Part 2, C: Pembro + paclitaxel + carboplatin→ Pembro + doxorubicin (or epirubicin) +cyclophosphamide

Doxorubicin hydrochloride 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

Also known as: ADRIAMYCIN®

Part 2, A: Pembrolizimab + patritumab deruxtecan → Pembrolizumab + paclitaxel + carboplatin; Part 2, B: Pembrolizumab + paclitaxel + carboplatin → Pembrolizumab + patritumab deruxtecan; Part 2, C: Pembro + paclitaxel + carboplatin→ Pembro + doxorubicin (or epirubicin) +cyclophosphamide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead
• Daiichi Sankyo: collaborator

Study Sites (17)

UCLA Hematology/Oncology - Parkside ( Site 0021)

Santa Monica, California, 90404, United States

RECRUITING

Orchard Healthcare Research Inc. ( Site 0006)

Skokie, Illinois, 60077, United States

RECRUITING

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

Billings, Montana, 59102, United States

RECRUITING

Northwest Cancer Specialists (Compass Oncology) ( Site 8003)

Tigard, Oregon, 97223, United States

RECRUITING

SCRI Oncology Partners ( Site 7000)

Nashville, Tennessee, 37203, United States

RECRUITING

Texas Oncology - DFW ( Site 8000)

Dallas, Texas, 75246, United States

RECRUITING

Houston Methodist Hospital ( Site 0022)

Houston, Texas, 77030, United States

RECRUITING

Virginia Oncology Associates (VOA) ( Site 8001)

Norfolk, Virginia, 23502, United States

RECRUITING

Seoul National University Hospital ( Site 2400)

Seoul, 03080, South Korea

RECRUITING

Severance Hospital, Yonsei University Health System ( Site 2402)

Seoul, 03722, South Korea

RECRUITING

Asan Medical Center ( Site 2401)

Seoul, 05505, South Korea

RECRUITING

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

Badalona, Catalonia, 08916, Spain

RECRUITING

Clinica Universidad de Navarra ( Site 1703)

Madrid, Madrid, Comunidad de, 28027, Spain

RECRUITING

Hospital Universitario Reina Sofia ( Site 1702)

Córdoba, 14004, Spain

RECRUITING

Taichung Veterans General Hospital ( Site 2502)

Taichung, 407, Taiwan

RECRUITING

National Cheng Kung University Hospital ( Site 2503)

Tainan, 704, Taiwan

RECRUITING

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

Taipei, 112, Taiwan

RECRUITING

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Conditions

Breast Neoplasms

Interventions

patritumab deruxtecan; pembrolizumab; Paclitaxel; Carboplatin; Doxorubicin; Epirubicin; Cyclophosphamide; Capecitabine; olaparib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Central Study Contacts

Toll Free Number

CONTACT

1-888-577-8839; Trialsites@msd.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part 1 is non-randomized. Part 2 is randomized 1:1:1.

Study Record Dates

• First Submitted: January 21, 2025
• First Posted: January 28, 2025
• Study Start: March 20, 2025
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2034
• Last Updated: May 20, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share

Locations

KR (3); US (8); TW (3); ES (3)