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)
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)
Merck Sharp & Dohme LLC
372 participants
Mar 20, 2025
INTERVENTIONAL
Conditions
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.
Eligibility
Inclusion Criteria6
- 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 Criteria13
- 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
Interventions
Administered via IV infusion as neoadjuvant treatment
Administered via IV infusion as neoadjuvant treatment in Part 1 and via IV infusion as neoadjuvant and adjuvant treatment in Part 2
Administered via IV infusion as neoadjuvant treatment
Administered via IV infusion as neoadjuvant treatment
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
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
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
Administered via oral tablets as an option for adjuvant treatment for participants with residual disease in Part 2
Administered via oral tablets as an option for adjuvant treatment for participants with germline BRCA mutations and residual disease in Part 2
Locations(17)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT06797635