This research study is a Phase II clinical trial. Phase II clinical trials test the safety
and effectiveness of an investigational drug to learn whether the drug works in treating a
specific disease. "Investigational" means that the drug is being studied.
This research study involves an experimental study treatment. The names of the study drugs
involved in this study is:
- Sacituzumab govitecan (SG)
- Pembrolizumab (combination therapy with SG)
The study is a umbrella study multi-arm phase II study of neoadjuvant SG-based therapy in
patients with localized BC. The first cohort involves SG monotherapy. After the monotherapy
cohort completes enrollment, the combination therapy cohort (SG with pembrolizumab) for
patients with localized BC will open.
Future planned arms include SG with/without pembrolizumab for patients with Hormone Receptor
positive (HR+) breast cancer and inflammatory breast cancer (IBC).
The research study procedures include screening for eligibility and study treatment including
evaluations and follow up visits.
- Eligible participants will receive Sacituzumab govitecan for up to 12 weeks.
- This can be followed by standard chemotherapy at the discretion of the treating
physician.
- It is expected that about 50 people will take part in this research study.
The U.S. Food and Drug Administration (FDA) has not approved Sacituzumab govitecan as a
treatment for patients with metastatic TNBC.
Sacituzumab govitecan (SG) is an antibody-drug conjugate which means it's made up of an
antibody attached to an anticancer drug. An antibody is a protein normally made the immune
system. Sacituzumab govitecan is believed to work by binding the antibody portion of the drug
in the tumor(s) while the anticancer drug portion works to prevent cancer cells from
growing/spreading.
After the SG monotherapy cohort completes enrollment, the combination therapy cohort (SG with
immunotherapy) will open.
Inclusion Criteria:
- Female or male patients ≥ 18 years of age.
- Histologically confirmed diagnosis of invasive breast cancer, previously untreated.
- Participants must have biopsy proven ER negative (ER-), PR negative (PR-), HER2
negative (HER2-), invasive breast cancer. ER, PR, and HER2 positivity would be
determined per ASCO/CAP guidelines by institutional (local) assessment. Patients with
multi-focal and multicentric disease are eligible provided all histologically examined
lesions are ER-/PR-/HER2- (local assessment). The need to biopsy additional lesions is
at the discretion of the treating physician. Patients with bilateral invasive breast
cancer are eligible provided all histologically examined lesions are ER-/PR-/HER2-
(local assessment).
- Primary tumor (at least one lesion) 1 cm or greater measured by radiological imaging.
Regional lymph node AJCC (v7) TNM stages N0-N2. If node positive, any primary tumor
size is permissible. Absence of distant metastatic disease (AJCC TNM stage M0).
Staging scans are not required and are per discretion of the treating physician.
- Pre- and postmenopausal women are eligible.
- ECOG performance status = 0, 1 (Karnofsky ≥60%, see Appendix A)
- Ability to understand and the willingness to sign a written informed consent form
(ICF). Patient has signed the ICF prior to any screening procedures being performed
and is able to comply with protocol requirements, including research biopsy.
- Patient has adequate bone marrow and organ function as defined by the following
laboratory values at screening:
- Absolute neutrophil count (ANC) ≥ 1,500 per mm3
- Platelets ≥ 100,000 per mm3
- Hemoglobin ≥9.0 g/dL
- INR ≤1.5
- Serum creatinine <1.5 mg/dL or creatinine clearance ≥50 mL/min
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <2.5 x ULN.
- Total bilirubin ≤1.5 x ULN or in patients with well-documented Gilbert's Syndrome
direct bilirubin ≤1.5 x ULN.
Exclusion Criteria:
- Inflammatory breast cancer, or locally recurrent breast cancer
- Participants currently receiving systemic therapy for any other malignancy or having
received systemic therapy for a malignancy in the preceding 3 years.
- Uncontrolled inter-current illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia,or psychiatric illness/social situations that would limit compliance with
study requirements.
- Clinically significant, uncontrolled heart disease and/or cardiac reppolarization
abnormality including any of the following:
- History of angina pectoris, symptomatic pericarditis, coronary artery bypass
graft (CABG) or myocardial infarction within 6 months prior to study entry.
- History of cardiac failure, known cardiomyopathy (LVEF < 50%; new LVEF assessment
is not specifically required for this trial), significant/symptomatic
bradycardia, Long QT syndrome, family history of idiopathic sudden death or
congenital long QT syndrome or any of the following:
- Known risk to prolong the QT interval or induce Torsade's de Pointes.
- Uncorrected hypomagnesemia or hypokalemia.
- Systolic Blood Pressure (SBP) >160 mmHg or <90 mmHg.
- Bradycardia (heart rate <50 at rest), by ECG or pulse. On screening, inability to
determine the QTcF interval on the ECG (i.e.: unreadable or not interpretable) or QTcF
>470 screening ECG
- Pregnant or breast-feeding women are excluded from this study because the safety of
study medications is not established.
- Known HIV-positive participants on combination antiretroviral therapy are ineligible.
- These participants are at increased risk of lethal infections when treated with
marrow-suppressive therapy. Separate HIV testing for this trial is not required.
Similarly, separate Hepatitis B or C testing for this trial is not required, but
patients with known (or history) of hepatitis B positive, or hepatitis C positive
infection will be excluded
