Inclusion Criteria:
- Ability to understand and the willingness to sign a written informed consent document
- Metastatic triple negative breast cancer (TNBC), as defined by:
- Estrogen receptor (ER) and progesterone receptor (PR) negative as defined as ER <
10% and PR < 10% by immunohistochemistry according to American Society of
Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines for
hormone receptor testing
- HER2 non-amplified per ASCO/CAP guidelines, defined as:
- IHC score 0/1+
- IHC 2+ and in situ hybridization (ISH) non-amplified with a ratio of HER2 to
CEP17 < 2.0, and if reported, average HER2 gene copy number < 4
signals/cells; or
- ISH non-amplified with a ratio of HER2 to CEP17 <2.0, and if reported,
average HER2 gene copy number < 4 signals/cells
- Participants must have at least one measurable site of disease as defined by Response
Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 that is amenable to biopsy
- Prior therapies for metastatic breast cancer
- Frontline patients who have not received prior systemic therapy for metastatic
breast cancer are eligible
- Patients who have received =< 2 prior chemotherapy regimens for metastatic breast
cancer are eligible
- Participants must have fully recovered from the acute toxic effects of all prior
treatment to grade 1 or less, except alopecia and =< grade 2 neuropathy which are
allowed
- Participants must have a life expectancy >= 16 weeks
- Participant must have Eastern Cooperative Oncology Group (ECOG) performance status =<
1
- Participant must consent to undergo a pre-treatment screening biopsy for enrollment
and subsequent biomarker analyses
- Participants must consent to undergo one mandatory on-study tumor biopsy following a 2
week induction treatment of olaparib. A second on-study biopsy at time of disease
progression is optional, but not mandatory
- Participants must not have had prior immunotherapy with anti-PD-L1, including
durvalumab anti-PD-1, anti-CTLA4 or similar drugs in the metastatic setting
- Participants may have received prior immunotherapy in the adjuvant setting, provided
- No documented disease progression on immunotherapy
- Treatment with immunotherapy was > 1 year from enrollment on study
- Participants must not have received previous treatment with PARP inhibitors, including
olaparib
- Hemoglobin >= 10.0 g/dL (measured within 28 days prior to administration of study
treatment) with no blood transfusion in the past 28 days
- Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (measured within 28 days prior to
administration of study treatment)
- Platelet count >= 100 x 10^9/L (measured within 28 days prior to administration of
study treatment)
- Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (measured within 28
days prior to administration of study treatment)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT])
=< 2.5 x institutional upper limit of normal unless liver metastases are present in
which case they must be =< 5 x ULN (measured within 28 days prior to administration of
study treatment)
- Participants must have creatinine clearance estimated of >= 51 mL/min using the
Cockcroft-Gault equation or based on a 24 hour urine test (measured within 28 days
prior to administration of study treatment)
- Female participants of childbearing potential must have a negative urine or serum
pregnancy test within 72 hours prior to receiving the first dose of study medication.
If the urine test is positive or cannot be confirmed as negative, a serum pregnancy
test will be required
- Female participants of childbearing potential agree to use adequate methods of
contraception starting with the first dose of study therapy through 60 days after the
last dose of study therapy. Participants of childbearing potential are those who are
not proven postmenopausal. Postmenopausal is defined as:
- Amenorrheic for 1 year or more following cessation of exogenous hormonal
treatments
- Luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in the
post menopausal range for women under 50
- Radiation-induced oophorectomy with last menses > 1 year ago
- Chemotherapy-induced menopause with > 1 year interval since last menses
- Surgical sterilization (bilateral oophorectomy or hysterectomy)
- Male participants must agree to use an adequate method of contraception starting with
the first dose of study therapy through 60 days after the last dose of study therapy
- Participants must not have received live vaccines within 30 days prior to the first
dose of immunotherapy. Examples of live vaccines include, but are not limited to, the
following: measles, mumps, rubella, chicken pox, shingles, yellow fever, rabies,
Bacillus Calmette-Guerin (BCG), and typhoid (oral) vaccine. Seasonal influenza
vaccines for injection are generally killed virus vaccines and are allowed; however,
intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are
not allowed. Patients, if enrolled, should not receive live vaccine whilst receiving
immunotherapy and up to 30 days after the last dose of immunotherapy
Exclusion Criteria:
- Currently participating and receiving study therapy or has participated in a study of
an investigational agent and received study therapy or used an investigation device
within 4 weeks of first dose of treatment.
- Individuals in the follow-up phase of a prior investigational study may
participate as long as it has been 4 weeks since last dose of the previous
investigational agent of device
- Participants with germline BRCA mutated TNBC will be excluded
- Other malignancy unless curatively treated with no evidence of disease for >= 5 years
except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer
of the cervix, ductal carcinoma in situ (DCIS), stage 1, grade 1 endometrial
carcinoma. Participants with a history of localized triple negative breast cancer may
be eligible, provided they completed their adjuvant chemotherapy more than three years
prior to registration, and that the participant remains free of recurrent or
metastatic disease
- Participants with myelodysplastic syndrome/acute myeloid leukemia or with features
suggestive of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML)
- Participant received prior chemotherapy within the past 28 days, prior targeted
therapies within the past 14 days, or radiation (except for palliative reasons) within
the past 3 weeks, prior to first day of treatment"
- Participants with known active central nervous system (CNS) metastases and/or
carcinomatous meningitis
- Participants with previously treated brain metastases may participate provided they
are stable (without evidence of progression by imaging [confirmed by computed
tomography (CT) scan if CT used at prior imaging, or confirmed by magnetic resonance
imaging (MRI) if MRI was used at prior imaging] for at least four weeks prior to the
first dose of trial treatment and any neurologic symptoms have returned to baseline),
have no evidence of new or enlarging brain metastases, and are not using steroids for
at least 7 days prior to trial treatment. This exception does not include
carcinomatous meningitis which is excluded regardless of clinical stability
- Participants unable to swallow orally administered medication and participants with
gastrointestinal disorders likely to interfere with absorption of the study medication
- Participants with visceral crisis defined as severe organ dysfunction as assessed by
signs and symptoms, laboratory studies, and rapid progression of disease
- Active infection requiring systemic antibiotic therapy. Participants requiring
systemic antibiotics for infection must have completed therapy before treatment is
initiated
- Participants considered a poor medical risk due to a serious, uncontrolled medical
disorder, non-malignant systemic disease or active, uncontrolled infection. Examples
include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3
months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal
cord compression, superior vena cava syndrome, extensive interstitial bilateral lung
disease on high resolution computed tomography (HRCT) scan or any psychiatric
illness/social situation that prohibits obtaining informed consent
- Resting electrocardiography (ECG) indicating uncontrolled, potentially reversible
cardiac conditions, as judged by the investigator (e.g., unstable ischemia,
uncontrolled symptomatic arrhythmia, congestive heart failure, corrected QT interval
by Fridericia's correction formula (QTcF) prolongation > 500 ms, electrolyte
disturbances, etc.), or participants with congenital long QT syndrome
- Participants with a history of hypersensitivity reactions to study agent or their
excipients
- Participant is pregnant or breastfeeding, or expecting to conceive or father children
within the projected duration of the trial, starting with the screening visit through
120 days after the last dose of trial treatment
- Involvement in the planning and/or conduct of the study
- Judgment by the investigator that the patient should not participate in the study if
the patient is unlikely to comply with study procedures, restrictions and requirements
- DURVALUMAB DRUG-SPECIFIC EXCLUSION CRITERIA:
- Participant has evidence of interstitial lung disease or active non-infectious
pneumonitis
- Major surgery within 2 weeks of starting study treatment and participants must have
recovered from any effects of any major surgery
- Note: Local surgery of isolated lesions for palliative intent is acceptable per
investigator discretion
- Active infection including tuberculosis (clinical evaluation that includes clinical
history, physical examination and radiographic findings, and tuberculosis [TB] testing
in line with local practice), hepatitis B (known positive hepatitis B virus [HBV]
surface antigen [HBsAg] result), hepatitis C, or human immunodeficiency virus
(positive human immunodeficiency virus [HIV] 1/2 antibodies). Participants with a past
or resolved HBV infection (defined as the presence of hepatitis B core antibody
[anti-HBc] and absence of HBsAg) are eligible. Participants positive for hepatitis C
(HCV) antibody are eligible only if polymerase chain reaction is negative for HCV
ribonucleic acid (RNA)
- History of active primary immunodeficiency
- Current or prior use of immunosuppressive medication within 14 days before the first
dose of durvalumab, with the exceptions of intranasal and inhaled corticosteroids or
systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of
prednisone, or an equivalent corticosteroid. The following are exceptions to this
criterion:
- Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra
articular injection)
- Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of
prednisone or its equivalent
- Steroids as premedication for hypersensitivity reactions (e.g., CT scan
premedication)
- Active or prior documented autoimmune or inflammatory disorders (including
inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with
the exception of diverticulosis], systemic lupus erythematosus, sarcoidosis syndrome,
or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid
arthritis, hypophysitis, uveitis, etc.]). The following are exceptions to this
criterion:
- Participants with vitiligo or alopecia
- Participants with hypothyroidism (e.g., following Hashimoto syndrome) stable on
hormone replacement
- Any chronic skin condition that does not require systemic therapy
- Participants without active disease in the last 5 years may be included but only
after consultation with the study physician
- Participants with celiac disease controlled by diet alone
- History of allogenic bone marrow transplant or double umbilical cord blood
transplantation
