Principal Investigator
Enrollment Status
Clinical Trial ID
Clinical Trial Summary
The purpose of this study is to compare the efficacy of olaparib (MK-7339) plus pembrolizumab
(MK-3475) with chemotherapy plus pembrolizumab after induction with first-line chemotherapy
plus pembrolizumab in triple negative breast cancer (TNBC). The primary hypotheses are:
1. Olaparib plus pembrolizumab is superior to chemotherapy plus pembrolizumab with respect
to progression-free survival (PFS).
2. Olaparib plus pembrolizumab is superior to chemotherapy plus pembrolizumab with respect
to overall survival (OS).
As of Amendment 3, study enrollment is being discontinued. Participants who are receiving
benefit from the study intervention may continue treatment until criteria for discontinuation
are met. Participants who are on study treatment or in follow-up phase will no longer have
tumor response assessments by BICR.
Phase
Phase 2
Funding Agency/Sponsor
Industrial
Disease
Breast Cancer
Enrollment Eligibility
Inclusion Criteria:
Induction Period:
- Has locally recurrent inoperable TNBC that has not previously been treated with
chemotherapy and that cannot be treated with curative intent OR has metastatic TNBC
that has not been previously treated with chemotherapy
- Has been treated with anthracycline and/or a taxane in the neoadjuvant/adjuvant
setting, if they received systemic treatment in the neoadjuvant/adjuvant setting,
unless anthracycline and/or taxane was contraindicated or not considered the best
treatment option for the participant in the opinion of the treating physician
- Has measurable disease based on RECIST 1.1
- Has provided a recently obtained or archival (no more than 3 years old) core or
excisional biopsy of a tumor lesion not previously irradiated
- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 as
assessed within 7 days prior to the start of induction study treatment
- Has a life expectancy ≥27 weeks from the day of first study treatment
- Demonstrate adequate organ function within 10 days prior to the start of study
treatment
- A male participant must agree to be abstinent or use contraception and refrain from
donating sperm during the intervention period and for at least the time needed to
eliminate each study intervention (95 days for olaparib and chemotherapy; no
requirement for pembrolizumab)
- A female participant must not be pregnant or breastfeeding and must agree to the
following if is a woman of childbearing potential (WOCBP): have a negative pregnancy
test within 24 hours before the start of study treatment and agree to be abstinent or
use contraception and refrain from donating eggs (ova, oocytes) during the
intervention period and for at least the time needed to eliminate each study
intervention (180 days for olaparib and chemotherapy; 120 days for pembrolizumab)
Post-induction Period:
- Has received up to 6 cycles but not less than 4 cycles of induction therapy without
permanently discontinuing from pembrolizumab or both carboplatin and gemcitabine
- Has achieved complete response (CR), partial response (PR), or stable disease (SD)
based on RECIST 1.1 by Blinded Independent Central Review (BICR) at the Week 18
evaluation
- Is able to complete during post-induction at least the Cycle 1, Day 1 doses of
olaparib and pembrolizumab or the Cycle 1, Day 1 doses of at least one of the
chemotherapy agents being administered at the end of induction (carboplatin and/or
gemcitabine) in addition to pembrolizumab
- Has ECOG performance status of 0 or 1, as assessed within 7 days prior to the start of
post-induction study treatment
- Has no higher than Grade 1 toxicities related to induction therapy (excluding
alopecia) prior to randomization
Exclusion Criteria:
Induction Period:
- Has a known additional malignancy that is progressing or has required active treatment
within the past 5 years with the exception of basal cell carcinoma of the skin,
squamous cell carcinoma of the skin, or carcinoma in situ (eg, cervical cancer in
situ) that have undergone potentially curative therapy
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
(in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
immunosuppressive therapy within 7 days prior the first dose of study treatment
- Has an active autoimmune disease that has required systemic treatment in the past 2
years
- Has known active central nervous system (CNS) metastases and/or carcinomatous
meningitis
- Has myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or has features
suggestive of MDS/AML
- Has a history of (non-infectious) pneumonitis\interstitial lung disease that required
steroids or current pneumonitis\interstitial lung disease
- Has active, or a history of, interstitial lung disease
- Has a known history of active tuberculosis
- Has an active infection requiring systemic therapy
- Has a known history of human immunodeficiency virus (HIV) infection
- Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg]
reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is
detected) infection
- Has a history of class II-IV congestive heart failure or myocardial infarction within
6 months of first study treatment
- Has neuropathy ≥Grade 2
- Has not recovered (eg, to ≤Grade 1 or to baseline) from AEs due to a previously
administered therapy
- Has a known history of hypersensitivity or allergy to pembrolizumab, olaparib and any
of its components, and/or to any of the study chemotherapies (eg, carboplatin or
gemcitabine) and any of their components
- Has severe hypersensitivity (≥Grade 3) to the study treatments and/or any of their
excipients
- Has a known psychiatric or substance abuse disorder that would interfere with the
participant's ability to cooperate 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 180 days
after the last dose of study treatment
- Is a WOCBP who has a positive urine pregnancy test within 24 hours prior to
randomization or treatment allocation
- Has received prior therapy with either olaparib or any other poly adenosine
diphosphate ribose polymerase (PARP) inhibitor
- Has received prior radiotherapy within 2 weeks of start of study treatment
- Has received colony-stimulating factors (eg, granulocyte colony stimulating factor
[G-CSF], granulocyte macrophage colony stimulating factor [GM-CSF] or recombinant
erythropoietin) within 2 weeks prior to the first dose of study treatment
- Has had an allogenic tissue/solid organ transplant.
- Has received previous allogenic bone marrow transplant or double umbilical cord
transplantation (dUCBT)
- Has had major surgery within 2 weeks of starting study treatment or has not recovered
from any effects of any major surgery
- Has received a live or live-attenuated vaccine within 30 days prior to first study
treatment
- Is receiving any medication prohibited in combination with study chemotherapies unless
medication was stopped within 7 days prior to first study treatment
- Has received prior therapy with an 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 a study evaluating pembrolizumab regardless of treatment received
- 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
- Has presence of uncontrolled, potentially reversible cardiac conditions, as judged by
the investigator
- Has a history or current evidence of any condition (eg, cytopenia,
transfusion-dependent anemia, or thrombocytopenia), therapy, or laboratory abnormality
that might confound the results of the study, interfere with the participant's
involvement for the full duration of the study, or is not in the best interest of the
participant to be involved, in the opinion of the treating investigator
- Is either unable to swallow orally administered medication or has a gastrointestinal
disorder affecting absorption (eg, gastrectomy, partial bowel obstruction,
malabsorption)
- Is unlikely to comply with the study procedures, restrictions, and requirements of the
study; as judged by the investigator
Post-induction Period:
- Has severe hypersensitivity (≥Grade 3) to the study treatments and/or any of their
excipients
- Has permanently discontinued from both carboplatin and gemcitabine during induction
due to toxicity
- Has permanently discontinued from pembrolizumab during induction due to toxicity
- Has received less than 4 cycles of chemotherapy plus pembrolizumab during induction
- Is currently receiving either strong or moderate inhibitors of cytochrome P450
(CYP)3A4 that cannot be discontinued for the duration of the study
- Is currently receiving either strong or moderate inducers of CYP3A4 that cannot be
discontinued for the duration of the study