Gender
All
Age Group
18 Years and up
Accepting Healthy Volunteers
No
Inclusion Criteria:
1. Advanced breast cancer with locally recurrent chest wall disease not amenable to
surgical excision with curative intent.
1. Distant sites of disease are allowed
2. Prior radiation to the chest wall is not required
2. The following disease subtypes are eligible:
1. Triple negative disease (defined as ER < 10%, PR < 10%, HER2 negative)
2. Hormone receptor positive, HER2 negative disease with evidence of progression
on at least two prior lines of hormone therapy, unless, per treating
investigator's judgement, is not considered a candidate for further endocrine
therapy
3. HER2 positive disease with evidence of disease progression on trastuzumab,
pertuzumab, Trastuzumab emtansine (T-DM1), and oral tyrosine kinase inhibitor
unless contraindicated with no other HER2 targeted therapy options available.
Patients in this category will be classified by ER status
- Histologically confirmed HER2+ breast carcinoma, with HER2+ defined by in
situ hybridization (ISH) or fluorescence in situ hybridization (FISH) or
immunohistochemistry (IHC) methodology using standard criteria.
- Cardiac function must be determined within 4 weeks of study entry to be >=
institutional lower limit of normal (LLN) using echo or multiple gated
acquisition scan (MUGA).
3. Any number of prior lines of therapy are allowed. a Prior platinum based therapy is
allowed in the following settings:
- Treatment in the neoadjuvant and/or adjuvant setting without clear progression
of disease.
- Treatment in the metastatic setting without clear progression of disease. b
Neo/adjuvant treatment with a checkpoint inhibitor is allowed if the last
treatment was at least 12 months from the diagnosis of metastatic disease.
4. At least two weeks from last systemic therapy for breast cancer, with recovery of
all treatment related toxicity to grade 1 or less. Subjects with <= Grade 2
neuropathy are an exception to this criterion.
5. At least two weeks from last radiation therapy, with recovery of all treatment
related toxicity to grade 1 or less (excluding alopecia).
6. Prior CNS disease is allowed if stable for at least one month since whole brain
radiation therapy, and 2 weeks since stereotactic radiotherapy, and not requiring
steroids. Patients whose CNS disease was surgically treated may be enrolled if
stable for at least one month, and not requiring steroids.
7. Able to provide tissue from a newly obtained core or excisional biopsy of a chest
wall tumor lesion. Newly-obtained is defined as a specimen any time after the last
systemic or local therapy utilized to treat the disease. Subjects for whom
newly-obtained samples cannot be provided (e.g. inaccessible or subject safety
concern) may submit an archived specimen only upon agreement from the Sponsor.
8. Willing and able to provide written informed consent.
9. Greater than or equal to 18 years of age on day of signing informed consent.
10. Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal
to 2.
11. Adequate organ function as defined below within 10 business days of treatment
initiation:
- Absolute neutrophil count (ANC) >=1,000 /microliter (mcL)
- Platelets>=100,000 / mcL
- Hemoglobin ≥9 g/dL or ≥5.6 mmol/L without transfusion or erythropoietin (EPO)
dependency (within 7 days of assessment)
- Serum creatinine OR Measured or calculated* creatinine clearance (GFR can also
be used in place of creatinine or CrCl) <=1.5 X upper limit of normal (ULN) OR
>=60 mL/min for subject with creatinine levels > 1.5 X institutional ULN.
Creatinine clearance should be calculated per institutional standard.
- Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin <= ULN for subjects with
total bilirubin levels > 1.5 ULN
- Aspartate aminotransferase (AST) (SGOT) and Alanine aminotransferase (ALT)
(SGPT) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver metastases
- Albumin >2.5 g/dL
- International Normalized Ratio (INR) or Prothrombin Time (PT) <=1.5 X ULN
unless subject is receiving anticoagulant therapy as long as PT or PTT is
within therapeutic range of intended use of anticoagulants
- Activated Partial Thromboplastin Time (aPTT) <=1.5 X ULN unless subject is
receiving anticoagulant therapy as long as PT or PTT is within therapeutic
range of intended use of anticoagulants
12. Female subjects of childbearing potential should have a negative urine or serum
pregnancy 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.
13. Female subjects of childbearing potential should be willing to use an acceptable
form of birth control or be surgically sterile, or abstain from heterosexual
activity for the course of the study through 120 days after the last dose of study
medication (Reference Section 5.7.2). Subjects of childbearing potential are those
who have not been surgically sterilized or have not been free from menses for > 1
year.
14. Male subjects should agree to use an adequate method of contraception starting with
the first dose of study therapy through 120 days after the last dose of study
therapy.
Exclusion Criteria:
1. Treatment with an investigational agent within 4 weeks of the first dose of
treatment.
2. A diagnosis of immunodeficiency or is currently receiving systemic steroid therapy
at any dose or is receiving any other form of immunosuppressive therapy. Steroid
therapy is not allowed within 7 days prior to the first dose of trial treatment.
However, topical and intranasal corticosteroids are allowed, and not an exclusion
for participation.
3. Known active TB (Bacillus Tuberculosis). Patients with a distant history of
tuberculosis that was appropriately treated and have no evidence of active infection
are eligible to participate. Patients with a history of latent tuberculosis that was
appropriately treated are also eligible to participate.
4. Hypersensitivity to pembrolizumab or any of its excipients.
5. Hypersensitivity to carboplatin or cisplatin
6. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy
within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at
baseline) from adverse events due to a previously administered agent.
- Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion.
- Note: If subject received major surgery, they must have recovered adequately
from the toxicity and/or complications from the intervention prior to starting
therapy.
7. Has a known additional malignancy that is progressing or requires active treatment.
Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of
the skin that has undergone potentially curative therapy or in situ cervical cancer.
8. Has known active central nervous system (CNS) metastases and/or carcinomatous
meningitis.
9. Has active autoimmune disease that has required systemic treatment in the past 2
years (i.e., with use of disease modifying agents, corticosteroids or
immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or
physiologic corticosteroid replacement therapy for adrenal or pituitary
insufficiency, etc.) is not considered a form of systemic treatment.
10. Has a history of (non-infectious) pneumonitis/interstitial lung disease that
required steroids or has current pneumonitis/ interstitial lung disease
11. Has an active infection requiring systemic therapy.
12. Has a history or current evidence of any condition, therapy, or laboratory
abnormality that might confound the results of the trial, interfere with the
subject's participation for the full duration of the trial, or is not in the best
interest of the subject to participate, in the opinion of the treating investigator.
13. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
14. Is pregnant or breastfeeding, or expecting to conceive or father children within the
projected duration of the trial, starting with the pre-screening or screening visit
through 120 days after the last dose of trial treatment.
15. Prior checkpoint inhibitor therapy in the metastatic setting.
16. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
17. Has known active Hepatitis B virus (HBV) [e.g., hepatitis B surface antigen (HBsAg)
reactive] or Hepatitis C virus (HCV) [e.g., HCV ribonucleic acid (RNA),
[qualitative] is detected].
18. Has received a live vaccine or live-attenuated vaccine within 30 days prior to the
first dose of study drug. Administration of killed vaccines is allowed.