| Eligibility |
Inclusion Criteria:
- Written informed consent and any locally-required authorization obtained from the
patient prior to performing any protocol-related procedures, including Screening
evaluations.
- Females, =18 years at time of study entry.
- HLA-A2 positive by deoxyribonucleic acid (DNA) sequence analysis (by history or as
part of this study).
- Histopathological diagnosis of triple negative breast cancer(TNBC) (ductal, lobular,
mixed or metaplastic), defined as estrogen receptor (ER)<1%, progesterone receptor
(PR)<1%, and Human Epidermal growth factor Receptor 2 (HER2) negative according to
American Society of Clinical Oncology/College of American Pathologists guidelines by
local testing according to institutional standards. For tumors with equivocal
interpretation of receptor status (e.g. "weak" or "faint" staining, the Principal
Investigator will have final determination of triple negative status.
- Completed all planned therapy for Stage II or III TNBC (American Joint Committee on
Cancer, 7th Edition) meeting the following guidelines:
- received neoadjuvant chemotherapy with residual invasive disease at surgery
and/or completed adjuvant chemotherapy with or without radiation. (The patient
may have had adjuvant and/or neoadjuvant chemotherapy for their disease).
Adjuvant/neoadjuvant chemotherapy regimens must include at least 4 cycles of a
standard chemotherapy regimen, and generally this should include one of the
generally accepted standard regimens (including but not limited to:
Adriamycin/Cytoxan-Taxol, Taxotere/Cytoxan, Adriamycin/Cytoxan, or
Cytoxan/Methotrexate/Fluorouracil). For patients who received their standard
chemotherapy as part of a clinical trial, the regimen should include at least 4
cycles of therapy.
- All planned radiation therapy surgery for the treatment of the current cancer
should be complete (not including plastic or reconstructive surgery).
- Patients with local-regional recurrence without evidence of distant metastases
(no definite stage IV disease) who are treated with curative intent may be
eligible following completion of all surgery and/or chemotherapy and/or
radiotherapy. Such patients must have no evidence of residual disease by standard
clinical and radiological examination (per Investigator discretion) following
completion of curative intent treatment.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 (see Appendix B).
- Adequate normal organ and marrow function as defined below:
- Hemoglobin =9.0 g/dL.
- absolute neutrophil count (ANC) =1.5 109/L (=1500 per mm3).
- Platelet count =100 109/L (>100,000 per mm3).
- Serum bilirubin =1.5 institutional upper limit of normal (ULN). This will not
apply to patients with confirmed Gilbert's syndrome (persistent or recurrent
hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis
or hepatic pathology).
- aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =2.5 ULN.
- gamma-glutamyltransferase (GGT), lactate dehydrogenase (LDH), and alkaline
phosphatase =2.5 ULN.
- Serum creatinine clearance >40 mL/min by the Cockcroft-Gault formula 72 or by
24-hour urine collection for determination of creatinine clearance:
Females:
Creatinine Clearance (mL/min) = Weight (kg) x (140 - Age) 0.85 72 x serum creatinine
(mg/dL)
- Negative virology/serology for human immunodeficiency virus (HIV)-1, HIV-2, hepatitis
B (surface antigen), and hepatitis C.
- Female patients must either be of non-reproductive potential (i.e. post-menopausal by
history of age =60 years old and no menses for 1 year without an alternative medical
cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history
of bilateral oophorectomy) or must have a negative serum pregnancy test (ß-human
chorionic gonadotropin (HCG)) at the Screening visit. (If Screening visit pregnancy
test was completed within 7 days of first treatment visit it does not need to be
repeated. Patients with a negative pregnancy test at Screening beyond 7 days prior to
treatment, but who otherwise meet all other criteria, may be registered to study but
must have a repeat negative serum pregnancy test within 7 days of treatment and such
testing may be done on day of first treatment prior to administration).
- If not postmenopausal or surgically sterile, study patients must be willing to
practice at least one of the following methods of birth control for at least a
menstrual cycle before and after study drug administration: (1) Total abstinence from
sexual intercourse with a male; (2) Sexual intercourse with vasectomized male partner;
(3) Other acceptable forms of birth control (condoms, contraceptive sponge, diaphragm
or vaginal ring with spermicide or cream); (4) Use of an intrauterine contraceptive
device.
- Patient is willing and able to comply with the protocol for the duration of the study
including undergoing treatment and scheduled visits and examinations including follow
up.
Exclusion Criteria:
- Involvement in the planning and/or conduct of the study (applies to both AstraZeneca
staff and/or staff at the study site).
- Previous enrollment in the present study.
- Receipt of the last dose or treatment of anti-cancer therapy for the current cancer
(chemotherapy, radiotherapy, surgery, immunotherapy, endocrine therapy, targeted
therapy, biologic therapy, tumor embolization, monoclonal antibodies, other
investigational agent) =4 weeks (6 weeks for nitrosoureas or mitomycin C) or >6 months
prior to first dose of study drug.
- Any unresolved clinically significant treatment related toxicity of =Grade 1
intensity, as assessed using the National Cancer Institute (NCI) Common Terminology
Criteria for Adverse Events (CTCAE), from previous anti-cancer therapy. Patients with
irreversible toxicity (eg, hearing loss, peripherally neuropathy) or reversible
toxicity (eg, alopecia) that is not reasonably expected to be exacerbated by the
investigational product and is not expected to interfere with study participation may
be included.
- Participation in another clinical study with an investigational product during the
previous 4 weeks.
- Any previous treatment with a programmed cell death protein 1 (PD1) or PD-L1
inhibitor, including durvalumab.
- Stage IV disease, confirmed by biopsy or unequivocal radiographic evidence (note:
staging scans are not required, but should be performed at treating physician
discretion in accordance with standard guidelines).
- Mucinous or tubal histology or other good prognosis histology.
- Ongoing or planned systemic anti-cancer therapy or radiation therapy.
- Pregnant or nursing.
- Known hypersensitivity to any component of the investigational product (PVX-410,
durvalumab, or any excipient).
- Mean QT interval corrected for heart rate (QTc) =470 ms calculated from 3
electrocardiograms (ECGs) using Frediricia's Correction.
- Active or prior documented active autoimmune disease that has required systemic
treatment. Note: Patients with vitiligo, Grave's disease, or psoriasis not requiring
systemic treatment (within the past 2 years) are not excluded.
- Current or prior use of immunosuppressive medication within 28 days before the first
dose of durvalumab, with the exceptions of intranasal and inhaled corticosteroids or
systemic (oral or iv) corticosteroids at physiological doses, which are not to exceed
10 mg/day of prednisone, or an equivalent corticosteroid.
- Active or prior documented inflammatory bowel disease (eg, Crohn's disease, ulcerative
colitis).
- History of primary immunodeficiency.
- History of allogeneic organ transplant.
- Uncontrolled intercurrent illness (including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable
angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active
bleeding diatheses including any patient known to have evidence of acute or chronic
hepatitis B, hepatitis C or HIV)
- Psychiatric illness/social situations that would limit compliance with study
requirements or compromise the ability of the patient to give written informed
consent.
- History or clinical evidence of any surgical or medical condition which the
Investigator judges as likely to interfere with the results of the study or pose an
additional risk in participating (eg, active or clinically significant history of
disease involving a major organ system-vascular, cardiac, pulmonary, hepatic,
gastrointestinal, gynecologic, hematologic, neurologic, neoplastic, renal, endocrine
or immunodeficiency, autoimmune or clinically significant active psychiatric
disorders).
- Known history of previous clinical diagnosis of tuberculosis
- Receipt of live attenuated vaccination within 30 days prior to study entry or within
30 days of receiving durvalumab
- Weight < 30 kg
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