Early Triple Negative Breast Cancer
Conditions
Keywords
Triple Negative Breast Cancer, Breast cancer, Neoadjuvant, Boserolimab, Pembrolizumab, Umbrella study
Brief summary
Researchers want to learn if giving boserolimab (MK-5890) with standard treatment (pembrolizumab and chemotherapy) before surgery can help treat triple negative breast cancer (TNBC). The goals of this study are to learn about the safety of boserolimab given with standard treatment before surgery and to learn if people tolerate it and how many people have no signs of cancer in the tissues and lymph nodes removed during surgery.
Detailed description
The umbrella design of this study provides the framework to evaluate the safety, tolerability and clinical activity of different investigational agents in participants with newly diagnosed, high-risk, early-stage TNBC who might benefit from adding these investigational agents to pembrolizumab plus chemotherapy.
Interventions
BIOLOGICALPembrolizumab
Neoadjuvant therapy - 200 mg intravenous (IV) infusion every 3 weeks (Q3W) for up to approximately 24 weeks Adjuvant therapy - 200 mg IV infusion Q3W or 400 mg IV infusion every 6 weeks (Q6W) for up to approximately 30 weeks.
DRUGPaclitaxel
80 mg/m\^2 by IV infusion every week for up to 12 weeks.
DRUGCarboplatin
AUC 1.5 mg/mL/min by IV infusion every week for up to 12 weeks.
DRUGDoxorubicin (hydrochloride)
60 mg/m\^2 by IV infusion Q3W for up to 12 weeks.
BIOLOGICALBoserolimab
30 mg by IV infusion every 6 weeks (Q6W) for up to 12 Weeks.
DRUGEpirubicin Hydrochloride
90 mg/m\^2 by IV infusion every 3 weeks (Q3W) for up to 12 weeks.
DRUGCyclophosphamide
600 mg/m\^2 by IV infusion every 3 weeks (Q3W) for up to 12 weeks.
DRUGCapecitabine
1000 mg/m\^2 to 1250 mg/m\^2 by oral administration twice a day (2 weeks on and 1 week off) for up to approximately 24 weeks.
DRUGOlaparib (if approved/available locally)
300 mg by oral administration twice a day for up to approximately 52 weeks.
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 tumor stage T1c, nodal stage N1-2, or tumor stage T2-4, nodal stage N0-2 * Has provided a core needle biopsy for tissue diagnosis of the current breast cancer less than 29 days prior to the date of informed consent * Has centrally confirmed diagnosis of BC that is triple-negative based on the American Society of Clinical Oncology/College of American Pathologists guidelines * Has Eastern Cooperative Oncology Group performance status of 0 or 1 performed within 28 days before treatment randomization * Has left ventricle ejection fraction of ≥50% as assessed by echocardiogram or multigated acquisition scan performed at screening * Has a history of exposure to anthracycline; participants can be eligible after completion of a Sponsor consultation form, if cumulative lifetime doses are as follows: Doxorubicin \<100 mg/m2, Epirubicin \<180 mg/m2, Mitoxantrone \<40 mg/m2, Idarubicin \<22.5 mg/m2. Note: If another anthracycline or more than one anthracycline has been used, the cumulative dose must not exceed the equivalent of 100 mg/m2 of doxorubicin
Exclusion criteria
The main
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with one or more adverse events (AEs) | Up to approximately 34 months | An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. |
| Number of participants who discontinue study intervention due to an AE | Up to approximately 27 months | An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. |
| Pathological complete response (pCR) rate at the time of definitive surgery | Up to approximately 9 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| pCR-no ductal carcinoma in situ (DCIS) rate at the time of definitive surgery | Up to approximately 9 months | 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. |
| Event-Free Survival (EFS) | Up to approximately 72 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. |
| Overall Survival (OS) | Up to approximately 72 months | OS is defined as the time from randomization to death due to any cause. |
Countries
Taiwan, United States
Contacts
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Outcome results
None listed