Triple-negative Breast Cancer
Conditions
Keywords
Pembrolizumab, Carboplatin, Docetaxel, Pegfilgrastim, breast cancer
Brief summary
The standard treatment for women with stage I, II, and III triple-negative breast cancer (TNBC) includes chemotherapy and surgery, with or without radiation therapy. However, because TNBC is usually more aggressive, harder to treat, and more likely to come back, it is associated with poor long-term outcomes (survival rates) when compared to other types of breast cancer. Therefore, researchers are studying how new drugs and treatment combinations can improve the outcome of patients with TNBC. This study will test effectiveness of immune therapy (Pembrolizumab is an immunotherapy that is expected to work with the body's immune system to help fight cancer) in combination with chemotherapy given before surgery.
Interventions
DRUGCarboplatin
Intravenous solution
DRUGDocetaxel
Intravenous solution
DRUGPembrolizumab
Intravenous solution
DRUGPegfilgrastim
Injectable product
Sponsors
Merck Sharp & Dohme LLC
University of Kansas Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Ability of participant to understand this study, and participant willingness to sign a written informed consent for this trial. * Histologically confirmed stage I , II or III TNBC (triple-negative breast cancer). * No previous definitive ipsilateral breast surgery for the current breast cancer. * No previous chemotherapy, endocrine therapy, or radiation therapy with therapeutic intent for this cancer. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Adequate organ function * Adequate cardiac function * A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: * Not a woman of childbearing potential (WOCBP) * A WOCBP who agrees to follow contraceptive guidelines. Key
Exclusion criteria
* Current or anticipated use of other investigational agents while participating in this study. * Participant has received chemotherapy, radiotherapy, or surgery for the treatment of breast cancer. * Participant has metastatic disease. * Participant has inflammatory breast cancer. * Participants with concomitant or previous malignancies within the last 5 years are excluded from the study. * Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. ductal carcinoma in situ (DCIS), carcinoma in situ of the cervix) that have undergone potential curative therapy are not excluded. * History of allergic reactions or hypersensitivity attributed to compounds of similar chemical or biologic composition to agents used in this study. * Participant has received prior therapy with an anti-programmed death (PD) -1, anti-PD-ligand (L)-1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory thymus lymphocyte (T-cell) receptor. * Subject has received a live vaccine within 30 days prior to the first dose of study drug. * Participant is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment * Participant has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of Pembrolizumab. * Has active autoimmune disease that has required systemic treatment in the past 2 years. * Has a history of (non-infectious) pneumonitis that required steroids, or has current pneumonitis. * Has an active infection requiring systemic therapy. * Has a known history of Human Immunodeficiency Virus (HIV). * Has a known history of Hepatitis B or known active Hepatitis C virus.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pathological Complete Response (pCR) Rate | Up to 25 weeks | Defined as the percentage of patients with PCR, as evidenced by absence of invasive disease in breast and axillary lymph nodes determined by histopathological examination. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Minimal Residual Disease (MRD) Rate | Up to 25 weeks | Defined as the percentage of patients with MRD, as evidenced by residual cancer burden (RCB) score of 0/1. Residual cancer burden score for each patient is calculated using surgical pathology parameters using an online tool (http://www3.mdanderson.org/app/medcalc/index.cfm?pagename=jsconvert3). |
| Percentage of Participants With Event-free Survival (EFS) as Assessed by Kaplan-Meier Method | Up to 3 years | Percentage of patients with EFS as assessed by Kaplan-Meier method. EFS is defined as time from diagnosis to first invasive locoregional or distant recurrence, study treatment-related death, or breast cancer-related death |
Countries
United States
Participant flow
Pre-assignment details
5 patients were found to be ineligible after enrollment and are not included in assessment for study outcomes.
Participants by arm
| Arm | Count |
|---|---|
| Experimental: Carboplatin & Docetaxel Plus Pembroluzimab Carboplatin (Area under the curve \[AUC\] 6 intravenously \[IV\]) and Docetaxel (75 milligrams per meter squared \[mg/m2\], IV) plus Pembrolizumab (200 milligrams \[mg\], IV) every 21 days for 6 cycles.
Pegfilgrastim 6 mg subcutaneous (SC) Day 2 of each cycle.
Carboplatin: Intravenous solution
Docetaxel: Intravenous solution
Pembrolizumab: Intravenous solution
Pegfilgrastim: Injectable product | 115 |
| Total | 115 |
Baseline characteristics
| Characteristic | Experimental: Carboplatin & Docetaxel Plus Pembroluzimab |
|---|---|
| Age, Continuous | 50 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 112 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Lymph node status Negative | 70 Participants |
| Lymph node status Positive | 45 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 20 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 91 Participants |
| Region of Enrollment United States | 115 Participants |
| Sex: Female, Male Female | 115 Participants |
| Sex: Female, Male Male | 0 Participants |
| T stage T1 | 21 Participants |
| T stage T2 | 73 Participants |
| T stage T3 | 21 Participants |
| T stage T4 | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 11 / 115 |
| other Total, other adverse events | 115 / 115 |
| serious Total, serious adverse events | 17 / 115 |
Outcome results
Primary
Pathological Complete Response (pCR) Rate
Defined as the percentage of patients with PCR, as evidenced by absence of invasive disease in breast and axillary lymph nodes determined by histopathological examination.
Time frame: Up to 25 weeks
Population: Evaluable for pathologic response
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Experimental: Carboplatin & Docetaxel Plus Pembroluzimab | Pathological Complete Response (pCR) Rate | 64 Participants |
Secondary
Minimal Residual Disease (MRD) Rate
Defined as the percentage of patients with MRD, as evidenced by residual cancer burden (RCB) score of 0/1. Residual cancer burden score for each patient is calculated using surgical pathology parameters using an online tool (http://www3.mdanderson.org/app/medcalc/index.cfm?pagename=jsconvert3).
Time frame: Up to 25 weeks
Population: Residual cancer burden (RCB) class available
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Experimental: Carboplatin & Docetaxel Plus Pembroluzimab | Minimal Residual Disease (MRD) Rate | 76 Participants |
Secondary
Percentage of Participants With Event-free Survival (EFS) as Assessed by Kaplan-Meier Method
Percentage of patients with EFS as assessed by Kaplan-Meier method. EFS is defined as time from diagnosis to first invasive locoregional or distant recurrence, study treatment-related death, or breast cancer-related death
Time frame: Up to 3 years
Population: Intention-to-treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Experimental: Carboplatin & Docetaxel Plus Pembroluzimab | Percentage of Participants With Event-free Survival (EFS) as Assessed by Kaplan-Meier Method | 86 Survival percentage by Kaplan-Meier |