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)
Status and phase
Enrolling
Phase 2
Conditions
Breast Cancer
Breast Neoplasms
Treatments
Drug: Epirubicin hydrochloride
Drug: Cyclophosphamide
Drug: Carboplatin
Drug: Doxorubicin hydrochloride
Biological: Pembrolizumab
Drug: Capecitabine
Drug: Paclitaxel
Drug: Olaparib
Biological: Patritumab deruxtecan
Study type
Interventional
Funder types
Industry
Identifiers
NCT06797635
1022-010
2024-514376-40-00 (Registry Identifier)
U1111-1307-7867 (Other Identifier)
MK-1022-010 (Other Identifier)
Details and patient eligibility
About
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.
Enrollment
372 estimated patients
Sex
All
Ages
18+ years old
Volunteers
No Healthy Volunteers
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
Trial design
Primary purpose
Treatment
Allocation
Randomized
Interventional model
Parallel Assignment
Masking
None (Open label)
372 participants in 4 patient groups
Part 1, A: Pembrolizimab + patritumab deruxtecan → Pembrolizumab + paclitaxel + carboplatin
Experimental group
Description:
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.
Treatment:
Biological: Patritumab deruxtecan
Drug: Paclitaxel
Biological: Pembrolizumab
Drug: Carboplatin
Part 2, A: Pembrolizimab + patritumab deruxtecan → Pembrolizumab + paclitaxel + carboplatin
Experimental group
Description:
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.
Treatment:
Biological: Patritumab deruxtecan
Drug: Olaparib
Drug: Paclitaxel
Drug: Capecitabine
Biological: Pembrolizumab
Drug: Doxorubicin hydrochloride
Drug: Carboplatin
Drug: Cyclophosphamide
Drug: Epirubicin hydrochloride
Part 2, B: Pembrolizumab + paclitaxel + carboplatin → Pembrolizumab + patritumab deruxtecan
Experimental group
Description:
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.
Treatment:
Biological: Patritumab deruxtecan
Drug: Olaparib
Drug: Paclitaxel
Drug: Capecitabine
Biological: Pembrolizumab
Drug: Doxorubicin hydrochloride
Drug: Carboplatin
Drug: Cyclophosphamide
Drug: Epirubicin hydrochloride
Part 2, C: Pembro + paclitaxel + carboplatin→ Pembro + doxorubicin (or epirubicin) +cyclophosphamide
Active Comparator group
Description:
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.
Treatment:
Drug: Olaparib
Drug: Paclitaxel
Drug: Capecitabine
Biological: Pembrolizumab
Drug: Doxorubicin hydrochloride
Drug: Carboplatin
Drug: Cyclophosphamide
Drug: Epirubicin hydrochloride
Trial contacts and locations
6
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Central trial contact
Toll Free Number
Data sourced from clinicaltrials.gov
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