Clinical trial NCT06797635: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Breast Neoplasms
Breast Cancer
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
Collaborators: name: Daiichi Sankyo
First posted: 2025-01-28
Enrollment: 372
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Part 1 is non-randomized. Part 2 is randomized 1:1:1.
Primary purpose: TREATMENT

Brief 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 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

Primary outcomes:
measure: Part 1: Number of Participants Experiencing an Adverse Event (AE)
timeFrame: Up to ~43 weeks
measure: Part 1: Number of Participants Who Experience One or More Dose-Limiting Toxicities (DLTs)
timeFrame: Up to 21 days
measure: Part 1: Number of Participants who Discontinued Study Treatment Due to an AE
timeFrame: Up to ~30 weeks
measure: Part 2: Pathological Complete Response (pCR) Rate Using the Definition of ypT0/Tis ypN0
timeFrame: Up to ~30 weeks
measure: Part 2: Number of Participants Experiencing an AE
timeFrame: Up to ~103 weeks
measure: Part 2: Number of Participants who Discontinued Study Treatment Due to an AE
timeFrame: Up to ~90 weeks
Secondary outcomes:
measure: Part 2: pCR-No Ductal Carcinoma in Situ (DCIS) Rate Using the Definition of ypT0 ypN0
timeFrame: Up to ~30 weeks
measure: Part 2: Event-Free Survival (EFS)
timeFrame: Up to ~100 months
measure: Part 2: Overall Survival (OS)
timeFrame: Up to ~100 months
measure: Part 2: Distant Progression or Distant Recurrence-Free Survival (DPDRFS)
timeFrame: Up to ~100 months
measure: Part 2: Residual Cancer Burden (RCB)
timeFrame: Up to ~30 weeks
Other outcomes:
Locations:
city: Skokie
country: United States
facility: Orchard Healthcare Research Inc. ( Site 0006)
state: Illinois
city: Billings
country: United States
facility: Intermountain Health St. Vincent Regional Hospital - Cancer Centers of Montana ( Site 0003)
state: Montana
city: Tigard
country: United States
facility: Northwest Cancer Specialists (Compass Oncology) ( Site 8003)
state: Oregon
city: Nashville
country: United States
facility: SCRI Oncology Partners ( Site 7000)
state: Tennessee
city: Dallas
country: United States
facility: Texas Oncology - DFW ( Site 8000)
state: Texas
city: Norfolk
country: United States
facility: Virginia Oncology Associates (VOA) ( Site 8001)
state: Virginia
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: