Principal Investigator
Enrollment Status
Clinical Trial ID
Clinical Trial Summary
The study will consist of two parts.
In Part 1, the safety of pembrolizumab (MK-3475) in combination with one of three different
chemotherapies will be assessed in the treatment of locally recurrent inoperable or
metastatic triple negative breast cancer (TNBC), which has not been previously treated with
chemotherapy.
In Part 2, the safety and efficacy of pembrolizumab plus background chemotherapy will be
assessed compared to the safety and efficacy of placebo plus background chemotherapy in the
treatment of locally recurrent inoperable or metastatic TNBC, which has not been previously
treated with chemotherapy.
The primary hypotheses are that:
1. the combination of pembrolizumab and chemotherapy prolongs Progression-Free Survival
(PFS) compared to placebo and chemotherapy in:
- all participants,
- participants with programmed cell death-ligand 1 (PD-L1) combined positive score
(CPS) ≥1 tumors, and
- participants with PD-L1 CPS ≥10 tumors, and
2. the combination of pembrolizumab and chemotherapy prolongs Overall Survival (OS)
compared to placebo and chemotherapy in:
- all participants,
- participants with PD-L1 CPS ≥1 tumors, and
- participants with PD-L1 CPS ≥10 tumors.
Phase
Phase 3
Funding Agency/Sponsor
Industrial
Disease
Breast Cancer
Enrollment Eligibility
Inclusion Criteria:
- Has locally recurrent inoperable breast cancer not previously treated with
chemotherapy and which cannot be treated with curative intent OR has metastatic breast
cancer not previously treated with chemotherapy.
- Has centrally confirmed TNBC, as defined by the most recent American Society of
Clinical Oncology/college of American Pathologists (ASCO/CAP) guidelines.
- Has completed treatment for Stage I-III breast cancer, if indicated, and ≥6 months
elapsed between the completion of treatment with curative intent (e.g., date of
primary breast tumor surgery or date of last adjuvant chemotherapy administration,
whichever occurred last) and first documented local or distant disease recurrence.
- Has been treated with (neo)adjuvant anthracycline, if they received systemic treatment
in the (neo)adjuvant setting, unless anthracycline was contraindicated or not
considered the best treatment option for the participant in the opinion of the
treating physician.
- Has measurable disease based on Response Evaluation Criteria in Solid Tumors version
1.1 (RECIST 1.1) as determined by local radiology review.
- Has provided recently or newly obtained core or excisional biopsy from a locally
recurrent inoperable or metastatic tumor lesion for central determination of TNBC
status and PD-L1 expression, unless contraindicated due to site inaccessibility and/or
participant safety concerns.
- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, as
assessed within 10 days prior to the start of study drug.
- Has a life expectancy ≥12 weeks from randomization.
- Demonstrates adequate organ function, within 10 days prior to the start of study drug.
- Female participants are eligible to participate if they are not pregnant or
breastfeeding AND they are not a woman of childbearing potential (WOCBP) OR is a WOCBP
using a contraceptive method that is highly effective or is abstinent from
heterosexual intercourse during the intervention period and for at least the time
needed to eliminate each study intervention after the last dose of study intervention
AND has a negative highly-sensitive pregnancy test ([urine or serum] as required by
local regulations) within 24 hours (urine) or 72 hours (serum) before the first dose
of study intervention.
- Male participants are eligible to participate if they agree to refrain from donating
sperm during the intervention period and for at least the time needed to eliminate
each study intervention after the last dose of study intervention PLUS be abstinent
from heterosexual intercourse OR must agree to use contraception unless confirmed to
be azoospermic.
Exclusion Criteria:
- Is currently participating in a clinical study and receiving an investigational agent
and/or using an investigational device, or has participated in a clinical study and
received an investigational agent and/or used an investigational device within 4 weeks
prior to randomization.
- Has not recovered (e.g., to ≤ Grade 1 or to baseline) from AEs due to a previously
administered therapy.
- Has neuropathy ≥ Grade 2.
- Has an active autoimmune disease that has required systemic treatment in the past 2
years (e.g., with use of disease modifying agents, corticosteroids, or
immunosuppressive drugs).
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any
other form of immunosuppressive therapy within 7 days prior to randomization.
- Has a known additional malignancy that progressed or required active treatment within
the last 5 years. Exceptions include basal cell carcinoma of the skin, squamous cell
carcinoma of the skin that has undergone potentially curative therapy, and in situ
cervical cancer.
- Has known active central nervous system (CNS) metastases and/or carcinomatous
meningitis. Participants with previously treated brain metastases may participate
provided they have stable brain metastases and did not receive chemotherapy for
metastatic breast cancer.
- Has history of (non-infectious) pneumonitis that required steroids or current
pneumonitis.
- Has active, or a history of, interstitial lung disease.
- Has a known history of active tuberculosis (TB).
- Has an active infection requiring systemic therapy.
- Has a history of Class II-IV congestive heart failure or myocardial infarction within
6 months of randomization.
- Has a known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the study.
- Is pregnant or breastfeeding, or expecting to conceive or father children within the
projected duration of the study, starting with the screening visit through 120 days
(or longer as specified by local institutional guidelines) after the last dose of
study drug.
- Has received prior therapy with an anti-programmed cell death 1 (anti-PD-1),
anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another co-inhibitory T
cell receptor (such as cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX-40,
CD137) or has previously participated in Merck pembrolizumab (MK-3475) clinical
studies.
- Has a known history of human immunodeficiency virus (HIV).
- Has known active hepatitis B or hepatitis C.
- Has received a live vaccine within 30 days prior to randomization.
- Has a known history of hypersensitivity or allergy to pembrolizumab and any of its
components and/or to any of the study chemotherapies (e.g., nab-paclitaxel,
paclitaxel, gemcitabine, or carboplatin) and any of their components.
- Is receiving any medication prohibited in combination with study chemotherapies as
described in the respective product labels, unless medication was stopped within 7
days prior to randomization.