Recruiting
Phase 2

Sacituzumab Govitecan & Pembrolizumab

Sponsor:

Dana-Farber Cancer Institute

Code:

NCT04468061

Conditions

Breast Cancer

Triple Negative Breast Cancer

PD-L1 Negative

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Sacituzumab Govitecan

Pembrolizumab

Study Details

Brief summary:

This research study involves testing the safety and efficacy of an investigational intervention for patients with triple-negative breast cancer (TNBC) that has spread, or metastasized, to other parts the body and is PD-L1-negative.

The names of the study interventions involved in this study are:

  • Sacituzumab govitecan (Trodelvy™;IMMU-132)
  • Pembrolizumab (Keytruda®; MK-3475)

Conditions

Breast Cancer

Triple Negative Breast Cancer

PD-L1 Negative

Study ID

NCT04468061

Start date

Jul 20, 2020

Status verified date

Apr, 2026

Completion date

Apr 1, 2029

Anticipated

Primary completion date

Apr 1, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • 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.
  • Estrogen-receptor and progesterone-receptor expression both ≤ 5% by immunohistochemistry (IHC), and HER2-negative status as determined by the current ASCO/CAP guidelines. If a patient has more than one histological result, the most recent sample will be considered for inclusion.
  • Participants must have PD-L1-negative metastatic breast cancer defined as less than 1% expression of PD-L1 on tumor-infiltrating immune cells (IC) by the PD-L1 IHC SP142 assay or a Combined Positive Score (CPS) less than 10 by the PD-L1 IHC 22C3 assay measured with standard of care testing.
  • Participants must be treatment-naïve in the metastatic setting.
  • Participants must have evaluable or measurable disease per RECIST 1.1. 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 (see Section 9 for more details). Participants must agree to a mandatory repeat biopsy 3-6 weeks after starting treatment, if tumor is safely accessible.
  • Prior chemotherapy: Participants must have received no prior chemotherapy for metastatic breast cancer and must have discontinued all chemotherapy at least 28 days prior to study treatment initiation. 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, unless otherwise specified per protocol, except alopecia can be any grade and neuropathy can be grade 2 or lower.
  • Prior biologic therapy: Patients must have received no prior biologic therapy for metastatic breast cancer and 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, unless otherwise specified per protocol.
  • Prior radiation therapy: Patients may have received prior radiation therapy. Radiation therapy must be completed at least 7 days prior to study treatment initiation, and all toxicities related to prior radiation therapy must have resolved to CTCAE v5.0 grade 1 or lower, unless otherwise specified per protocol. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
  • Previously treated brain metastases are permitted, with the following provisions:

  • Prior SRS should complete ≥ 7 days before study treatment initiation
  • Prior WBRT should complete ≥ 7 days before study treatment initiation.
  • Any corticosteroid use for brain metastases must have been discontinued for ≥ 7 days prior to study treatment initiation.
  • The subject is ≥ 18 years old.
  • ECOG performance status 0-1 (Karnofsky > 60%, see Appendix A).
  • 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, established and proper use of hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.
  • 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
  • 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 participant must be capable of understanding and complying with the protocol and willing to sign a written informed consent document.

Exclusion Criteria:

  • Has received prior systemic anti-cancer therapy, including investigational agents, within 4 weeks of study treatment initiation or during the course of this study (bisphosphonates and RANK ligand inhibitors are allowed).
  • Prior therapy with any anti-PD-1, PD-L1, or PD-L2 agent or sacituzumab govitecan (IMMU-132). Prior therapy with irinotecan or topoisomerase I-containing antibody drug conjugates at any time for early stage or metastatic disease.
  • Prior hypersensitivity to pembrolizumab or the excipients of pembrolizumab or sacituzumab govitecan (IMMU-132 therapy).
  • Known history of UDP-glucuronosyltransferase 1A1 (UGT1A1) \*28 allele homozygosity, which is associated with increased risk for neutropenia and diarrhea related to irinotecan. 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 symptoms.
  • 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 that required steroids or current pneumonitis.
  • 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 when treated with marrow-suppressive therapy. 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 enrollment.

Study Design

Enrollment

110 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Sacituzumab Govitecan + Pembrolizumab

Participants will receive Sacituzumab Govitecan + Pembrolizumab at a pre-determined dose during a 21 day cycle.

Sacituzumab Govitecan will be given on days 1 and 8 of the 21 day cycle Pembrolizumab will be given on day 1 of the 21 day cycle.

experimental: Sacituzumab Govitecan

Participants will receive Sacituzumab Govitecan at a pre-determined dose during a 21 day cycle.

Sacituzumab Govitecan will be given on days 1 and 8 of a 21-day cycle

experimental: Retreatment

Participants randomized to the combination arm (Sacituzumab Govitecan + Pembrolizumab) who stop with CR after at least 24 weeks of treatment may be eligible for additional pembrolizumab and/or sacituzumab govitecan therapy if they progress after stopping study treatment. This is termed the Second Course Phase and is only available if the study remains open and the subject meets conditions.

.

Interventions

Sacituzumab Govitecan

Intravenous Infusion

Pembrolizumab

Intravenous Infusion

Primary outcome measure

  • Progression Free Survival (PFS) [ Time Frame: 3 years ]

Central Contacts and Locations

Central contacts

Ana C Garrido-Castro, MD

617-632-6409Ana_Garrido-Castro@dfci.harvard.edu

Locations

Stamford Hospital

Recruiting

Stamford, Connecticut, United States, 06904

Contacts

K.M. Steve Lo, MD

slo@stamhealth.org

Principal Investigator:

K.M. Steve Lo, MD

Miami Cancer Institute at Baptist Health (Kendall)

Recruiting

Miami, Florida, United States, 33176

Contacts

Lauren Carcas, MD

laurencar@baptisthealth.net

Principal Investigator:

Lauren Carcas, MD

Miami Cancer Institute at Baptist Health

Recruiting

Plantation, Florida, United States, 33324

Contacts

Lauren Carcas, MD

laurencar@baptisthealth.net

Principal Investigator:

Lauren Carcas, MD

University of Chicago Medical Center

Recruiting

Chicago, Illinois, United States, 60637

Contacts

Rita Nanda, MD

rnanda@medicine.bsd.uchicago.edu

Principal Investigator:

Rita Nanda, MD

Eastern Maine Medical Center

Recruiting

Brewer, Maine, United States, 04412

Contacts

Sarah Sinclair, DO

ssinclair@emhs.org

Principal Investigator:

Sarah Sinclair, DO

Dana Farber Cancer Institute

Recruiting

Boston, Massachusetts, United States, 02215

Contacts

Ana C. Garrido-Castro, MD

617-632-6409Ana_Garrido-Castro@dfci.harvard.edu

Principal Investigator:

Ana C. Garrido-Castro, MD

DFCI @ Foxborough

Recruiting

Foxborough, Massachusetts, United States, 02035

Contacts

Natalie Sinclair, MD

Nsinclair1@partners.org

Principal Investigator:

Natalie Sinclair, MD

DFCI @ Milford Regional Hospital

Recruiting

Milford, Massachusetts, United States, 01757

Contacts

Natalie Sinclair, MD

nsinclair1@partners.org

Principal Investigator:

Natalie Sinclair, MD

DF/BWCC in Clinical Affiliation with South Shore Hospital

Recruiting

South Weymouth, Massachusetts, United States, 02190

Contacts

Thomas P O'Connor, MD

ThomasP_O'Connor@DFCI.HARVARD.EDU

Principal Investigator:

Thomas P O'Connor, MD

The University of North Carolina at Chapel Hill

Recruiting

Chapel Hill, North Carolina, United States, 27599

Contacts

Emily Ray, MD

emmi@ad.unc.edu

Principal Investigator:

Emily Ray, MD

The Christ Hospital Cancer Center

Recruiting

Cincinnati, Ohio, United States, 45219

Contacts

Julie Specht, MD

julie.specht@thechristhospital.com

Principal Investigator:

Julie Specht, MD

Ohio State University Medical Center

Recruiting

Columbus, Ohio, United States, 43212

Contacts

Margaret Gatti-Mays, MD

margaret.gatti-mays@osumc.edu

Principal Investigator:

Margaret Gatti-Mays, MD

University of Pennsylvania-Abramson Cancer Center

Recruiting

Philadelphia, Pennsylvania, United States, 19104

Contacts

Payal Shah, MD

payal.shah@pennmedicine.upenn.edu

Principal Investigator:

Payal Shah, MD

Medical University of South Carolina

Recruiting

Charleston, South Carolina, United States, 29425

Contacts

sivapira@musc.edu

Principal Investigator:

Abirami Sivapiragasam, MD

Sarah Cannon Research Institute

Recruiting

Chattanooga, Tennessee, United States, 37404

Contacts

Brooke R Daniel, MD

bdaniel@tnonc.com

Principal Investigator:

Brooke R Daniel, MD

More Information

Sponsor

Dana-Farber Cancer Institute

Last update posted

Apr 29, 2026

Last verified

Apr, 2026

Keywords

  • Breast Cancer
  • Triple Negative Breast Cancer
  • PD-L1 Negative

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-09. This information was provided to ClinicalTrials.gov by Dana-Farber Cancer Institute on 2026-04-29. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.