Breast Neoplasms, HR Low-Positive/HER2-Negative Breast Neoplasms, Triple Negative Breast Neoplasms
Conditions
Keywords
Programmed Cell Death-1 (PD1, PD-1), Programmed Cell Death 1 Ligand 1 (PDL1, PD-L1), Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2)
Brief summary
Researchers are looking for new ways to treat types of breast cancer that are both: * High-risk, which means the cancer may have a higher chance of getting worse or coming back after treatment * Early-stage, which means the cancer is in the breast or the lymph nodes around the breast The 2 types of breast cancer in this study are triple-negative breast cancer (TNBC) and hormone receptor (HR)-low positive/human epidermal growth factor receptor-2 (HER2) negative breast cancer. These cancers have zero or a low amount of a protein called HER2 and other proteins that attach to the hormones estrogen or progesterone. Sacituzumab tirumotecan (also known as sac-TMT or MK-2870), the study medicine, is a type of targeted therapy. A targeted therapy is a treatment that works to control how specific types of cancer cells grow and spread. The main goals of this study are to learn if people who receive sac-TMT, pembrolizumab, and chemotherapy: * Have fewer cancer cells found in the tumors and lymph nodes removed during surgery compared to those who receive only pembrolizumab and chemotherapy * Live longer without the cancer growing, spreading, or coming back compared to people who receive only pembrolizumab with chemotherapy
Interventions
BIOLOGICALSacituzumab tirumotecan
IV infusion
BIOLOGICALPembrolizumab
IV infusion
DRUGRescue Medication
Participants receive rescue medication at the investigators discretion, per approved product label. Recommended rescue medications are histamine -1 (H1) receptor agonist, histamine-2 (H2) receptor antagonist, acetaminophen or equivalent, dexamethasone or equivalent infusion, or steroid mouthwash (dexamethasone or equivalent).
DRUGCarboplatin
IV infusion
DRUGPaclitaxel
IV infusion
DRUGDoxorubicin
IV infusion
DRUGEpirubicin
IV infusion
DRUGCyclophosphamide
IV infusion
DRUGCapecitabine
Oral tablet
DRUGOlaparib
Oral tablet
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
The main inclusion criteria include but are not limited to the following: * Has previously untreated high-risk, early-stage, non-metastatic (M0) breast cancer (BC), defined as any of the following combined primary tumor (T) and regional lymph node (N) staging per AJCC 8th edition criteria as assessed by the physician investigator based on radiological and/or clinical assessment: * cT1c, N1-N2 * cT2, N0-N2 * cT3, N0-N2 * cT4a-d, N0-N2 * The participant must have a centrally confirmed diagnosis of BC that is triple-negative or HR-low+/HER2- (defined as estrogen receptor (ER)-low+ expression in 1% to 10% cells and HER2- as by the most recent American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines. * Provides a core needle biopsy from the primary breast tumor at screening to the central laboratory. * Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 performed within 28 days before Cycle1 Day 1 (C1D1). * Demonstrates adequate organ function.
Exclusion criteria
The main
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants with Pathological Complete Response (pCR) at the Time of Definitive Surgery | Up to approximately 30 weeks | pCR (ypT0/Tis ypN0) is defined as the absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes after completion of neoadjuvant systemic therapy per current American Joint Committee on Cancer (AJCC) staging criteria assessed by the local pathologist at the time of definitive surgery. |
| Event-Free Survival (EFS) | Up to approximately 92 months | EFS is defined as the time from randomization to disease progression that precludes surgery, local or distant recurrence, or death due to any cause, whichever occurs first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Up to approximately 115 months | OS is defined as the time from randomization to death due to any cause. |
| Percentage of Participants with pCR with No Ductal Carcinoma in Situ (pCR-no DCIS) at the Time of Definitive Surgery | Up to approximately 30 weeks | pCR-no ductal carcinoma in situ (DCIS) (ypT0 ypN0) is defined as the absence of residual invasive and in situ cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes after completion of neoadjuvant systemic therapy per current AJCC staging criteria assessed by the local pathologist at the time of definitive surgery. |
| Percentage of Participants with pCR at the Time of Definitive Surgery (High-risk, early-stage, TNBC subset) | Up to approximately 30 weeks | pCR (ypT0/Tis ypN0) is defined as the absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes after completion of neoadjuvant systemic therapy per current American Joint Committee on Cancer (AJCC) staging criteria assessed by the local pathologist at the time of definitive surgery. The pCR will be presented for the subset of participants who enrolled with high-risk, early-stage, TNBC. |
| Event-Free Survival (EFS) (High-risk, early-stage, TNBC subset) | Up to approximately 92 months | EFS is defined as the time from randomization to disease progression that precludes surgery, local or distant recurrence, or death due to any cause, whichever occurs first. The EFS will be presented for the subset of participants who enrolled with high-risk, early-stage, TNBC. |
| Overall Survival (OS) (High-risk, early-stage, TNBC subset) | Up to approximately 115 months | OS is defined as the time from randomization to death due to any cause. |
| Distant Progression or Distant Recurrence-Free Survival (DPDRFS) | Up to approximately 92 months | DPDRFS is defined as the time from randomization to first distant progression or distant recurrence event as assessed by investigator, or death due to any cause, whichever occurs first. |
| Change from Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status-Quality of Life Score | Baseline and up to approximately 3 years | The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the QoL of cancer patients. Participant responses to Item 30 (""How would you rate your overall quality of life during the past week?") is scored on a 7-point scale (1=Very Poor to 7=Excellent). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher value indicates a better level of function. The change from baseline in EORTC QLQ-C30 Item 30 score will be reported. |
| Change from Baseline in EORTC QLQ-C30 Physical Functioning Score | Baseline and up to approximately 3 years | The EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life of cancer patients. Participant responses to questions about their physical functioning are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better level of physical functioning. |
| Change from Baseline in EORTC QLQ-C30 Role Functioning Score | Baseline and up to approximately 3 years | The EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life of cancer patients. Participant responses to questions about their role functioning are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better level of physical functioning. |
| Change from Baseline in EORTC QLQ-C30 Fatigue Score | Baseline and up to approximately 3 years | The EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life of cancer patients. Participant responses to questions about their fatigue are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A lower score indicates a better level of function. |
| Change from Baseline in EORTC QLQ Breast Cancer 42 (BR42) Systemic Therapy Side Effects Score | Baseline and up to approximately 3 years | The EORTC QLQ-BR42 is a 42-item questionnaire to assess the overall quality of life of breast cancer patients. Participant responses to questions about their systemic therapy side effects are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A lower score indicates a lower level of side effects. |
| Number of Participants Who Experience One or More Adverse Events (AEs) | Up to approximately 67 weeks | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. |
| Number of Participants Who Discontinue Study Treatment Due to an AE | Up to approximately 54 weeks | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. |
Countries
Argentina, Australia, Belgium, Brazil, Canada, Chile, China, Colombia, Czechia, Finland, France, Germany, Greece, Guatemala, Hong Kong, Hungary, India, Israel, Italy, Japan, Malaysia, New Zealand, Norway, Peru, Philippines, Poland, Portugal, Romania, Singapore, South Africa, South Korea, Spain, Sweden, Taiwan, Thailand, Turkey (Türkiye), Ukraine, United Kingdom, United States, Vietnam
Contacts
CONTACTToll Free Number
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Outcome results
None listed