This is a prospective two-stage single arm phase II study to be conducted in conformance with
Good Clinical Practices.
This study will enrol 53 patients, based on a two steps Simon's design.
Patients will entry into the study if the following conditions will be satisfied:
- BRCA1/2 germline mutations.
- Metastatic disease with measurable lesions will be evaluated by computed tomography or
by PET (Positron Emission Tomography) scan.
- Patients must have received anthracycline and taxanes before entry into the study.
Patients will be treated with Carboplatin AUC6 (Area Under The Curve) EV (endovenous) every 3
weeks in combination with Pembrolizumab 200 mg EV every 3 weeks for 6 cycles. Afterwards, the
Pembrolizumab will recontinued with the same schedule until unacceptable toxicity or disease
The primary endpoint will be Objective Responses Rate (ORR) (complete answers + partial
answers) evaluated according to the RECIST criteria.
1. Be willing and able to provide written informed consent/assent for the trial.
2. Be 18 years of age on day of signing informed consent.
3. Patients must have metastatic confirmed breast cancer
4. Disease progression by radiological techniques within 12 months prior to signing
5. Documented mutation in BRCA1 or BRCA2 genes that is predicted to be deleterious or
suspected deleterious (unknown significance variants)
6. Have measurable disease based on RECIST 1.1.
7. Prior chemotherapy with anthracyclines and taxanes has to be administered in
neoadjuvant or adjuvant setting.
8. Be willing to provide tissue from a newly obtained core or excisional biopsy of a
tumor lesion. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days)
prior to initiation of treatment on Day 1. Subjects for whom newly-obtained samples
cannot be provided (e.g. inaccessible or subject safety concern) may submit an
9. Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
10. Life expectancy of greater than 3 months
11. Demonstrate adequate organ function. All screening labs should be performed within 10
days of treatment initiation.
12. Female subject 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 must be willing to use an adequate method of
contraception as outlined in Section 5.111.2 - Contraception, for the course of the
study through 120 days after the last dose of study medication.
Note: Abstinence is acceptable if this is the usual lifestyle and preferred
contraception for the subject.
14. Male subjects of childbearing potential must agree to use an adequate method of
contraception as outlined in Section 5.11.2- Contraception, starting with the first
dose of study therapy through 120 days after the last dose of study therapy.
Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception
for the subject.
1. Is currently participating and receiving study therapy or has participated in a study
of an investigational agent and received study therapy or used an investigational
device within 4 weeks of the first dose of treatment.
2. Has a benign variant of BRCA1/2 genes
3. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any
other form of immunosuppressive therapy within 7 days prior to the first dose of trial
4. Has a known history of active Bacillus Tuberculosis
5. Hypersensitivity to pembrolizumab or any of its excipients.
6. Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study
Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events
due to agents administered more than 4 weeks earlier.
7. 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 and
may qualify for the study.
- Note: If subject received major surgery, they must have recovered adequately from
the toxicity and/or complications from the intervention prior to starting
8. 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.
9. Has known active central nervous system (CNS) metastases and/or carcinomatous
meningitis. Subjects with previously treated brain metastases may participate provided
they are stable (without evidence of progression by 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.
10. 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 (eg., thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
form of systemic treatment.
11. Has a history of (non-infectious) pneumonitis that required steroids or current
12. Has an active infection requiring systemic therapy.
13. 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.
14. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
15. 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.
16. Has received prior therapy with an anti-PD-1 (anti-programmed cell Death-1),
anti-PD-L1, or anti-PD-L2 agent.
17. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
18. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV
(Hepatitis C Virus) RNA [qualitative] is detected).
19. Has received a live vaccine within 30 days of planned start of study therapy. Note:
Seasonal influenza vaccines for injection are generally inactivated flu vaccines and
are allowed; however intranasal influenza vaccines (e.g., Flu-Mist) are live
attenuated vaccines, and are not allowed.