This is a randomized open-label phase 2 study to evaluate the efficacy and safety (as
assessed by pCR) of the NANT Neoadjuvant TNBC Vaccine regimen (experimental arm) compared to
the SoC dose-dense regimen of doxorubicin/cyclophosphamide followed by paclitaxel (control
arm).
Treatment will be administered in 2 phases, a neoadjuvant phase and a postoperative phase.
The neoadjuvant phase will be 18 weeks for patients enrolled in the experimental arm and 16
weeks for those enrolled in the control arm.
Following the neoadjuvant phase, all subjects will undergo determination of their current
response status and appropriate breast surgery and node dissection after which assessment for
pCR will be conducted following completion of neoadjuvant systemic therapy. Pathologists
interpreting surgical specimens for pCR assessment will be blinded to the treatment arm.
All subjects, regardless of whether or not they have achieved a pCR, will then enter the
postoperative phase where they will receive adjuvant treatment. A small portion of the
corresponding neoadjuvant therapy, either nab-paclitaxel or paclitaxel, will be administered
as adjuvant treatment postoperatively. Adjuvant treatment will continue in the postoperative
phase until the subject experiences unacceptable toxicity (not correctable with dose
reduction), withdraws consent, or if the Investigator feels it is no longer in the subject's
best interest to continue treatment.
Inclusion Criteria:
1. Age ≥ 18 years.
2. Able to understand and provide a signed informed consent that fulfills the relevant
IRB or Independent Ethics Committee (IEC) guidelines.
3. Histologically confirmed stage II or III TNBC. Subjects must be treatment naïve. TNBC
is defined as breast cancer that lacks estrogen receptor (ER) and progesterone
receptor (PgR) expression, and human epidermal growth factor receptor 2 (HER2)
overexpression and/or amplification.
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
5. Have at least 1 measurable lesion of ≥ 1.0 cm.
6. Must have a recent FFPE tumor biopsy specimen and be willing to release the specimen
for prospective and exploratory tumor molecular profiling. If an historic specimen is
not available, the subject must be willing to undergo a biopsy during the screening
period, if considered safe by the Investigator.
7. Must be willing to provide blood samples prior to the start of treatment on this study
for prospective tumor molecular profiling and exploratory analyses.
8. Ability to attend required study visits and return for adequate follow-up, as required
by this protocol.
9. Agreement to practice effective contraception for female subjects of child-bearing
potential and non-sterile males. Female subjects of child-bearing potential must agree
to use effective contraception for up to 1 year after completion of therapy, and
non-sterile male subjects must agree to use a condom for up to 4 months after
treatment. Effective contraception includes surgical sterilization (eg, vasectomy,
tubal ligation), two forms of barrier methods (eg, condom, diaphragm) used with
spermicide, intrauterine devices (IUDs), and abstinence.
Exclusion Criteria:
1. Serious uncontrolled concomitant disease that would contraindicate the use of the
investigational drug used in this study or that would put the subject at high risk for
treatment-related complications.
2. Systemic autoimmune disease (eg, lupus erythematosus, rheumatoid arthritis, Addison's
disease, and autoimmune disease associated with lymphoma).
3. History of organ transplant requiring immunosuppression.
4. History of or active inflammatory bowel disease (eg, Crohn's disease and ulcerative
colitis).
5. Inadequate organ function, evidenced by the following laboratory results:
1. Absolute neutrophil count (ANC) < 1,000 cells/mm^3.
2. Platelet count < 75,000 cells/mm^3.
3. Uncorrectable grade 3 anemia (hemoglobin < 8 g/dL).
4. Total bilirubin greater than the upper limit of normal (ULN; unless the subject
has documented Gilbert's syndrome).
5. Aspartate aminotransferase (AST [SGOT]) or alanine aminotransferase (ALT [SGPT])
> 2.5 × ULN (> 5 × ULN in subjects with liver metastases).
6. Alkaline phosphatase (ALP) levels > 2.5 × ULN (> 5 × ULN in subjects with liver
metastases, or >10 × ULN in subjects with bone metastases).
7. Serum creatinine > 2.0 mg/dL or 177 μmol/L.
8. Serum anion gap > 16 mEq/L or arterial blood with pH < 7.3.
6. Uncontrolled hypertension (systolic > 160 mm Hg and/or diastolic > 110 mm Hg) or
clinically significant (ie, active) cardiovascular disease, cerebrovascular
accident/stroke, or myocardial infarction within 6 months prior to first study
medication; unstable angina; congestive heart failure of New York Heart Association
grade 2 or higher; or serious cardiac arrhythmia requiring medication.
7. Serious myocardial dysfunction defined by echocardiogram (ECHO) as absolute LVEF 10%
below the institution's lower limit of predicted normal.
8. Dyspnea at rest due to complications of advanced malignancy or other disease requiring
continuous oxygen therapy.
9. Positive results of screening test for human immunodeficiency virus (HIV).
10. Current chronic daily treatment (continuous for > 3 months) with systemic
corticosteroids (dose equivalent to or greater than 10 mg/day methylprednisolone),
excluding inhaled steroids. Short-term steroid use to prevent IV contrast allergic
reaction or anaphylaxis in subjects who have known contrast allergies is allowed.
11. Known hypersensitivity to any component of the study medication(s).
12. Subjects taking any medication(s) (herbal or prescribed) known to have an adverse drug
reaction with any of the study medications.
13. Concurrent or prior use of a strong cytochrome P450 (CYP)3A4 inhibitor (including
ketoconazole, itraconazole, posaconazole, clarithromycin, indinavir, nefazodone,
nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole, and grapefruit
products) or strong CYP3A4 inducers (including phenytoin, carbamazepine, rifampin,
rifabutin, rifapentin, phenobarbital, and St John's Wort) within 14 days before study
day 1.
14. Concurrent or prior use of a strong CYP2C8 inhibitor (gemfibrozil) or moderate CYP2C8
inducer (rifampin) within 14 days before study day 1.
15. Participation in an investigational drug study or history of receiving any
investigational treatment within 14 days prior to screening for this study, except for
testosterone-lowering therapy in men with prostate cancer.
16. Assessed by the Investigator to be unable or unwilling to comply with the requirements
of the protocol.
17. Concurrent participation in any interventional clinical trial.
18. Pregnant and nursing women.
