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)

Official title

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)

Overview

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 outcome measures

• Part 1: Number of Participants Experiencing an Adverse Event (AE) [Time frame: Up to ~43 weeks]
• Part 1: Number of Participants Who Experience One or More Dose-Limiting Toxicities (DLTs) [Time frame: Up to 21 days]
• Part 1: Number of Participants who Discontinued Study Treatment Due to an AE [Time frame: Up to ~30 weeks]
• Part 2: Pathological Complete Response (pCR) Rate Using the Definition of ypT0/Tis ypN0 [Time frame: Up to ~30 weeks]
• Part 2: Number of Participants Experiencing an AE [Time frame: Up to ~103 weeks]
• Part 2: Number of Participants who Discontinued Study Treatment Due to an AE [Time frame: Up to ~90 weeks]

Secondary outcome measures (5)

• Part 2: pCR-No Ductal Carcinoma in Situ (DCIS) Rate Using the Definition of ypT0 ypN0 [Time frame: Up to ~30 weeks]
• Part 2: Event-Free Survival (EFS) [Time frame: Up to ~100 months]
• Part 2: Overall Survival (OS) [Time frame: Up to ~100 months]
• Part 2: Distant Progression or Distant Recurrence-Free Survival (DPDRFS) [Time frame: Up to ~100 months]
• Part 2: Residual Cancer Burden (RCB) [Time frame: Up to ~30 weeks]

Eligibility 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 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 8 centers

• UCLA Hematology/Oncology - Parkside ( Site 0021) — Santa Monica
• Orchard Healthcare Research Inc. ( Site 0006) — Skokie
• Intermountain Health St. Vincent Regional Hospital - Cancer Centers of Montana ( Site 0003 — Billings
• Northwest Cancer Specialists (Compass Oncology) ( Site 8003) — Tigard
• SCRI Oncology Partners ( Site 7000) — Nashville
• Texas Oncology - DFW ( Site 8000) — Dallas
• Houston Methodist Hospital ( Site 0022) — Houston
• Virginia Oncology Associates (VOA) ( Site 8001) — Norfolk

South Korea · 3 centers

• Seoul National University Hospital ( Site 2400) — Seoul
• Severance Hospital, Yonsei University Health System ( Site 2402) — Seoul
• Asan Medical Center ( Site 2401) — Seoul

Spain · 3 centers

• Institut Català d'Oncologia (ICO) - Badalona ( Site 1700) — Badalona
• Clinica Universidad de Navarra ( Site 1703) — Madrid
• Hospital Universitario Reina Sofia ( Site 1702) — Córdoba

Taiwan · 3 centers

• Taichung Veterans General Hospital ( Site 2502) — Taichung
• National Cheng Kung University Hospital ( Site 2503) — Tainan
• Koo Foundation Sun Yat-Sen Cancer Center ( Site 2501) — Taipei

Identifiers

NCT: NCT06797635 · 1022-010 · MK-1022-010 · 2024-514376-40-00 · U1111-1307-7867

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗