Recruiting
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)
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…
ClinicalTrials.gov IDNCT06797635
PhasePHASE2
Enrollment372
SponsorMerck Sharp & Dohme LLC
Age18 Years
SexALL
Conditions studied
Breast Neoplasms, Breast Cancer
About this 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.
Interventions
- Biological: Patritumab deruxtecan — Administered via IV infusion as neoadjuvant treatment
- Biological: Pembrolizumab — Administered via IV infusion as neoadjuvant treatment in Part 1 and via IV infusion as neoadjuvant and adjuvant treatment in Part 2
- Drug: Paclitaxel — Administered via IV infusion as neoadjuvant treatment
- Drug: Carboplatin — Administered via IV infusion as neoadjuvant treatment
- 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
- 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
- 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
- Drug: Capecitabine — Administered via oral tablets as an option for adjuvant treatment for participants with residual disease in Part 2
- Drug: Olaparib — Administered via oral tablets as an option for adjuvant treatment for participants with germline BRCA mutations and residual disease in Part 2
Primary outcomes
- Part 1: Number of Participants Experiencing an Adverse Event (AE) (Up to ~43 weeks)
- Part 1: Number of Participants Who Experience One or More Dose-Limiting Toxicities (DLTs) (Up to 21 days)
- Part 1: Number of Participants who Discontinued Study Treatment Due to an AE (Up to ~30 weeks)
- Part 2: Pathological Complete Response (pCR) Rate Using the Definition of ypT0/Tis ypN0 (Up to ~30 weeks)
- Part 2: Number of Participants Experiencing an AE (Up to ~103 weeks)
- Part 2: Number of Participants who Discontinued Study Treatment Due to an AE (Up to ~90 weeks)
Eligibility information
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
- 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
Showing 10 of 17 reported sites. See the official listing for all locations.
Before you participate: Varda Clinical is an independent discovery tool, not the study sponsor or a medical provider. Eligibility can only be determined by the official study team. Discuss potential risks and benefits with a qualified healthcare professional.
Source: ClinicalTrials.gov. Record last refreshed by Varda Clinical: 2026-09-27.