Home › Trials › NCT06797635

New treatment approach for high-risk early-stage breast cancer

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)

PHASE2 · Merck Sharp & Dohme LLC · NCT06797635

This study is testing a new combination of treatments for people with high-risk early-stage triple-negative breast cancer to see if it can shrink tumors more than the usual treatment before surgery.

Quick facts

PhasePHASE2
Study typeInterventional
Enrollment372 (estimated)
Ages18 Years and up
SexAll
SponsorMerck Sharp & Dohme LLC (industry)
Drugs / interventionstrastuzumab, radiation, patritumab, pembrolizumab, chemotherapy
Locations17 sites (Santa Monica, California and 16 other locations)
Trial IDNCT06797635 on ClinicalTrials.gov

What this trial studies

This study investigates the safety and efficacy of combining patritumab deruxtecan and pembrolizumab with chemotherapy in patients with high-risk early-stage triple-negative breast cancer (TNBC) or hormone receptor-low positive/HER2 negative breast cancer. Participants will receive these treatments before surgery, and the study aims to determine if this combination leads to a greater reduction in cancer cells compared to standard treatment with pembrolizumab and chemotherapy alone. The study will also assess how well patients tolerate the new treatment regimen.

Who should consider this trial

Good fit: Ideal candidates include individuals with locally advanced, non-metastatic breast cancer that is triple-negative or hormone receptor-low positive/HER2 negative.

Not a fit: Patients with metastatic breast cancer or those whose cancer does not meet the specified criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could improve surgical outcomes and overall treatment effectiveness for patients with high-risk early-stage breast cancer.

How similar studies have performed: Other studies have shown promise in using combination therapies for breast cancer, suggesting potential for success with this novel approach.

Eligibility criteria

Show full inclusion / exclusion criteria 
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 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

Where this trial is running

Santa Monica, California and 16 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.

View on ClinicalTrials.gov →

Conditions: Breast Neoplasms, Breast Cancer

Last reviewed 2026-05-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.