This pilot study will provide preliminary data regarding the role of PIS in predicting the
benefit of immune checkpoint inhibition with or without chemotherapy for high risk patients
with TNBC and residual disease after effective neoadjuvant chemotherapy.
1. Biopsy proven TNBC:
- ER- and PR- defined as ≤5% cells stain positive
- HER2 negativity defined as:
- IHC 0, 1+ without in situ hybridization (ISH) HER2/neu chromosome 17 ratio
- IHC 2+ and ISH HER2/neu chromosome 17 ratio non-amplified with ratio less
than 2.0 and if reported average HER2 copy number < 6 signals/cells
2. Residual disease of 1.0 cm at least of the primary tumor and/or node positive disease
(at least ypN1)
3. Patients must have completed neoadjuvant chemotherapy; patients must NOT have received
capecitabine as part of their neoadjuvant therapy regimen. Acceptable preoperative
regimens include an anthracycline or a taxane, or both. Participants who received
preoperative therapy as part of a clinical trial may enroll. Participants may not have
received adjuvant chemotherapy after s urgery prior to randomization. .
Carboplatin-containing neoadjuvant chemotherapy is also allowed). Patients who cannot
complete all planned neoadjuvant treatment cycles for any reason are considered high
risk and therefore are eligible for the study if they have residual disease.
4. Recovery of all toxicities from previous therapies to at least grade 1, except
alopecia and ≤ grade 2 neuropathy which are allowed.
5. Must have completed definitive resection of primary tumor and have no evidence of
unresected or metastatic disease at the time of study entry
- Negative margins for both invasive and ductal carcinoma in situ (DCIS) are
desirable, however patients with positive margins may enroll if the treatment
team believes no further surgery is possible and patient has received
radiotherapy; patients with margins positive for lobular carcinoma in situ (LCIS)
- Either mastectomy or breast conserving surgery (including lumpectomy or partial
mastectomy) is acceptable
- Sentinel node biopsy post neoadjuvant chemotherapy (i.e. at the time of
definitive surgery) is allowed; axillary dissection is encouraged in patients
with lymph node involvement, but is not mandatory
6. ECOG PS 0-2
7. Patients must not be planning to receive concomitantly other biologic therapy,
hormonal therapy, other chemotherapy, surgery or other anti-cancer therapy except
radiation therapy while receiving treatment on this protocol.
8. At the time of registration (randomization), patients must have the following
laboratory results (obtained within 28 days prior to registration):
1. A serum TSH prior to registration to obtain a baseline value.
2. Patients must have adequate bone marrow function as evidenced by all of the
- ANC ≥ 1,500 microliter (mcL);
- Platelets ≥ 100,000/mcL;
- Hemoglobin ≥ 9 g/dL.
3. Patients must have adequate hepatic function as evidenced by the following:
- Total bilirubin ≤ 1.5 x institutional upper limit of normal (IULN) (except
Gilbert's Syndrome, who must have a total bilirubin < 3.0 mg/dL), and
- SGOT (AST) or SGPT (ALT) and alkaline phosphatase ≤ 2.5 x IULN.
4. Patients must have adequate renal function as evidenced by ONE of the following:
- Serum creatinine ≤ IULN OR
- Measured or calculated creatinine clearance ≥ 60 mL/min.
5. Women of childbearing potential must have a negative urine or serum pregnancy
test within 28 days prior to registration and within 24h prior to the start of
nivolumab. In addition, women of childbearing potential must agree to have a
pregnancy test every 4 weeks while on nivolumab.
9. Signed ICF
10. Age ≥18
1. Stage IV disease
2. Receipt of adjuvant chemotherapy
3. Diagnosis of other invasive cancer except for adequately treated cervix cancer or skin
cancer, or more than 5 years since other diagnosis of invasive cancer without current
evidence of disease
4. Previous exposure to capecitabine, fluorouracil or immunotherapy with anti-PD1,
anti-PDL1, anti-CTLA4 or similar drugs.
5. Active autoimmune disease that has required systemic treatment in the past 2 years;
replacement therapy is not considered a form of systemic therapy
6. TB, active hepatitis B, active hepatitis C or other active infection. Patients who
have completed curative therapy for HCV are eligible. Patients with known HIV
infection are eligible if they meet each of the following 3 criteria: CD4 counts ≥ 350
mm3; serum HIV viral load of < 25,000 IU/ml and treated on a stable antiretroviral
7. History of (non-infectious) pneumonitis that required steroids or evidence of active
8. Uncontrolled disease
9. Chronic use of systemic steroids
10. Live vaccine within 30 days prior to registration.
11. Incapacity to provide consent or to follow clinical trial procedures
12. Pregnancy, lactation, or planning to be pregnant
Patients with microsatellite unstable tumors will not be excluded as immunotherapy as
adjuvant therapy is not standard for these patients but we will prospective collect this