The research study procedures include: screening for eligibility, research blood collections,
at least two research biopsies, paired research stool collections, and study treatment
including evaluations and follow up visits.
The names of the study interventions involved in this study are:
- Sacituzumab govitecan (IMMU-132)
- Pembrolizumab (Keytruda®; MK-3475)
- Questionnaires/Data Collection/Sample Collection
Participants will be randomized into one of two groups. Group A: Sacituzumab govitecan
(IMMU-132) and Pembrolizumab Group B: Pembrolizumab
Participants will receive study treatment for as long they are benefiting from the therapy.
Participants will be followed for the rest of their lives. It is expected that about 110
people will take part in this research study
This research study is a Phase II clinical trial. Phase II clinical trials test the safety
and effectiveness of an investigational drug or a combination of investigational drugs to
learn whether the drug or drug combination works in treating a specific disease.
"Investigational" means that the drug or drug combination is being studied. The U.S. Food and
Drug Administration (FDA) has not approved Sacituzumab Govitecan for your specific disease,
but it has been approved for other uses. The U.S. Food and Drug Administration (FDA) has not
approved Pembrolizumab for your specific disease but it has been approved for other uses.
- Participants must have histologically or cytologically confirmed invasive breast
cancer with unresectable locally advanced or metastatic disease. Participants without
pathologic or cytologic confirmation of metastatic disease should have unequivocal
evidence of metastasis from physical examination or radiologic evaluation, i.e.
visible chest wall disease or metastases on imaging meeting standard radiology
criteria (i.e. lymph nodes larger than 1 cm in the short axis diameter).
- Participants must have HR-positive, HER2-negative breast cancer (ER>1% and/or, PR>1%,
HER2-negative per ASCO CAP guidelines) on local pathology review. If a patient has
more than one histological result, the most recent sample will be considered for
- Participants must have PD-L1-positive breast cancer defined as 1 or greater expression
of PD-L1 on the combined positive score (CPS) including both tumor and immune cells
determined by central testing of a fresh or archival tumor biopsy with the PD-L1
immunohistochemistry 22C3 assay. This testing will be performed centrally.
- Participants must have either progressed on or within 12 months of adjuvant endocrine
therapy or have progressed on at least one line of endocrine therapy for metastatic
disease, and be considered appropriate candidates for chemotherapy.
- Participants must have evaluable or measurable disease per RECIST 1.1. For instance,
patients with bone only disease will be allowed to participate.
- Participants must agree to undergo a research biopsy, if tumor is safely accessible,
at baseline. Previously collected archival tissue will also be obtained on all
participants. Tissue needs to be located and availability confirmed at time of
registration Participants must agree to a mandatory repeat biopsy 3-6 weeks after
starting treatment, if tumor is safely accessible.
- Prior hormonal therapy: Hormonal therapy must have been discontinued ≥14 days prior to
initiation of study therapy. However, continuation of ovarian suppression is allowed.
- Prior chemotherapy: Participants may have received 0-1 prior chemotherapeutic regimens
for metastatic breast cancer and must have been off treatment with chemotherapy for at
least 14 days prior to study treatment initiation. If a prior chemotherapy was given
for less than 1 cycle, it will not be counted as a prior line. No prior irinotecan or
topoisomerase I-containing antibody drug conjugates in the metastatic or neo/adjuvant
setting are allowed. All toxicities related to prior chemotherapy must have resolved
to CTCAE v5.0 grade 1 or lower, except alopecia can be any grade and neuropathy can be
grade 2 or lower.
- Prior biologic therapy: Patients must have discontinued all biologic therapy at least
28 days prior to study treatment initiation. All toxicities related to prior biologic
therapy must have resolved to CTCAE v5.0 grade 1 or lower.
- Prior targeted therapy: Targeted therapy must have been discontinued ≥ 14 days prior
to initiation of study therapy. All toxicities related to prior targeted therapy must
have resolved to CTCAE v5.0 grade 1 or lower.
- Prior radiation therapy: Patients may have received prior radiation therapy. Radiation
therapy must be completed at least 14 days prior to the initiation of study treatment
(at least 7 days for SRS), and all toxicities related to prior radiation therapy must
have resolved to CTCAE v5.0 grade 1 or lower, unless otherwise specified in 3.1.16. A
1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to
- Previously treated brain metastases are permitted, with the following provisions:
- Prior SRS should complete ≥ 7 days before study treatment initiation
- Prior WBRT should complete ≥ 14 days before study treatment initiation.
- Any corticosteroid use for brain metastases must have been discontinued for ≥ 7
days prior to study treatment initiation.
- Participants on bisphosphonates or RANK ligand inhibitors may continue receiving
therapy during study treatment and also may initiate therapy with these agents on
study if clinically indicated.
- The subject is ≥ 18 years old.
- ECOG performance status 0-1 (Karnofsky > 60%).
- Participants must have normal organ and marrow function as defined below:
- Absolute neutrophil count ≥1,000/mcL
- Platelets ≥100,000/mcL
- Hemoglobin ≥ 9.0 g/dl
- INR/PT/aPTT ≤1.5 × ULN unless participant is receiving anticoagulant therapy as
long as PT or aPTT is in therapeutic range of anticoagulant
- Total bilirubin ≤1.5 × institutional upper limit of normal (ULN) (or ≤2.0 x ULN
in patients with documented Gilbert's Syndrome)
- AST(SGOT)/ALT(SGPT) ≤2.5 × institutional ULN or ≤5 × institutional ULN for
participants with documented liver metastases
- Serum creatinine ≤1.5 × institutional ULN OR creatinine clearance ≥ 30 mL/min/
1.73m2 for participants with creatinine levels above institutional ULN.
- Female subjects of childbearing potential must have a negative serum or urine
pregnancy test within 2 weeks prior to study treatment initiation. Childbearing
potential is defined as participants who have not reached a postmenopausal state (≥ 12
continuous months of amenorrhea with no identified cause other than menopause) and
have not undergone surgical sterilization (removal of ovaries and/or uterus).
- Women of childbearing potential (WOCBP) must agree to use an adequate method of
contraception. Contraception is required starting with the first dose of study
medication through 180 days (6 months) after the last dose of study medication.
Examples of contraceptive methods with a failure rate of < 1% per year include
bilateral tubal ligation, male sterilization, and copper intrauterine devices.
Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation
methods) and withdrawal are not acceptable methods of contraception. Hormonal
contraceptives are contraindicated for HR+ breast cancer.
- Males who are sexually active with WOCBP must agree to follow instructions for
method(s) of contraception for the duration of study treatment with pembrolizumab and
3 months after the last dose of study treatment
- The participant must be capable of understanding and complying with the protocol and
willing to sign a written informed consent document.
- Concurrent administration of any other anti-cancer therapy, including investigational
agents, within 4 weeks of study treatment initiation and during the course of this
study (endocrine therapies, CDK4/6 inhibitors, capecitabine, bisphosphonates, and RANK
ligand inhibitors are allowed).
- Prior therapy with any anti-PD-1, PD-L1, or PD-L2 agent or sacituzumab govitecan.
Prior therapy with irinotecan or topoisomerase I-containing antibody drug conjugates
at any time for early stage or metastatic disease.
- Prior hypersensitivity to the excipients of pembrolizumab or sacituzumab govitecan
- Known history of UDP-glucuronosyltransferase 1A1 (UGT1A1) *28 allele homozygosity,
which is associated with increased risk for neutropenia and diarrhea related to
Note: Concurrent administration of strong UGT1A1 inhibitors or inducers is not allowed
during the course of the study
- Known brain metastases that are untreated, symptomatic, or require therapy to control
- Major surgery within 2 weeks prior to study treatment initiation. Patients must have
recovered from any effects of any major surgery.
- Uncontrolled, significant intercurrent or recent illness including, but not limited
to, ongoing or active infection, uncontrolled non-malignant systemic disease,
uncontrolled seizures, or psychiatric illness/social situation that would limit
compliance with study requirements in the opinion of the treating investigator.
- Participant has a medical condition that requires chronic systemic steroid therapy (>
10 mg of prednisone daily or equivalent) or any other form of immunosuppressive
medication (including disease modifying agents) and has required such therapy in the
last 2 years. Replacement therapy (e.g. thyroxine, insulin, or physiologic
corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is
not considered a form of systemic therapy.
- Participant has documented history of autoimmune disease or syndrome that currently
requires systemic steroids or immunosuppressive agents.
- History of (non-infectious) pneumonitis/interstitial lung disease that required
steroids or current pneumonitis/interstitial lung disease.
- Individuals with a history of a second malignancy are ineligible except for the
following circumstances. Individuals with a history of other malignancies are eligible
if they have been disease-free for at least 3 years or are deemed by the investigator
to be at low risk for recurrence of that malignancy. Individuals with the following
cancers that have been diagnosed and treated within the past 3 years are eligible:
cervical/prostate carcinoma in situ, superficial bladder cancer, non-melanoma cancer
of the skin. Patients with other cancers diagnosed within the past 3 years and felt to
be at low risk of recurrence should be discussed with the study principal investigator
to determine eligibility.
- Participant has a known history of human immunodeficiency virus (HIV), Hepatitis B
(defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C
virus (defined as detected HCV RNA [qualitative]) infection. HIV-positive participants
are ineligible due to the potential for pharmacokinetic interactions of combination
antiretroviral therapy with study drugs and the increased risk of fatal infections.
Note: No testing for HIV, Hepatitis B, or Hepatitis C is required unless mandated by
local health authority.
- The participant has received a live vaccine within 28 days prior to study treatment
initiation. Examples of live vaccines include, but are not limited to, the following:
measles, mumps, rubella, varicella/zoster, yellow fever, rabies, BCG, and typhoid
vaccine. The use of the inactivated seasonal influenza vaccine is allowed.
- Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the study, interfere with the subject's
participation for the full duration of the study, or is not in the best interest of
the subject to participate, in the opinion of the treating investigator.
- It is unknown whether pembrolizumab is excreted in human milk. Since many drugs are
excreted in human milk, and because of the potential for serious adverse reactions in
the nursing infant, participants who are breast-feeding are not eligible for