Sacituzumab Govitecan +/- Pembrolizumab in Metastatic TNBC

STATUS

Recruiting
End date

Jun 1, 2026
participants needed

110
sponsor

Dana-Farber Cancer Institute

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Updated on 19 February 2024

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cancer

estrogen

breast cancer

corticosteroids

measurable disease

metastasis

pembrolizumab

gilbert's syndrome

neutrophil count

liver metastasis

anticoagulants

oophorectomy

bisphosphonate

progesterone

irinotecan

tubal ligation

brain metastases

invasive breast cancer

immunohistochemistry

triple-negative breast cancer

mk-3475

immunomodulators

anticoagulant therapy

alopecia

copper

aptt

neuropathy

stage iv breast cancer

cns disease

immunostimulant

periodic abstinence

whole brain radiotherapy

programmed cell death 1 ligand 1

brain metastasis

central nervous system disease

keytruda

sacituzumab govitecan

adjuvant

hair thinning

HER2

central nervous system disorder

triple negative breast neoplasms

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 (IMMU-132)
Pembrolizumab (Keytruda; MK-3475)

Description

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 approved Sacituzumab Govitecan for metastatic triple-negative breast cancer, but it is currently approved only for patients who have had 2 or more prior regimens for metastatic disease. The U.S. Food and Drug Administration (FDA) has not approved Pembrolizumab for metastatic triple-negative breast cancer but it has been approved for other uses.

In this research study, we are:

Studying Sacituzumab Govitecan alone or in combination with Pembrolizumab as a possible treatment for patients with metastatic triple-negative breast cancers that are PD-L1-negative.
Sacituzumab Govitecan is composed of a chemotherapy drug, called Irinotecan, which is attached to an antibody. Antibodies are proteins normally made by the immune system that bind to substances that don't belong in the body to prevent harm. The antibody in this study binds to certain types of cancer tumors, including triple-negative breast tumors.
Pembrolizumab is an immunotherapy, called an anti-PD-1 or a checkpoint inhibitor, and is an antibody (a type of human protein) designed to allow the body's own immune system to seek out and destroy tumors. It has been used in previous research studies to treat breast cancer, where it has been shown to be effective.
The overall goal of this study is to evaluate the effectiveness of either Sacituzumab Govitecan alone or in combination with Pembrolizumab, in delaying the worsening of triple-negative breast cancers that are PD-L1-negative.

The research study procedures include: screening for eligibility, research blood collections, at least two research biopsies, paired research stool collections, questionnaires, data collection, and study treatment including evaluations and follow up visits.

Participants will be randomized into one of two groups.

Group A: Sacituzumab Govitecan on days 1 and 8 and Pembrolizumab on day 1 of a 21-day cycle
Group B: Sacituzumab Govitecan alone on days 1 and 8 of a 21-day cycle

Participants will receive study treatment for as long as they are benefitting from this therapy. Participants will be followed for the rest of their life.

It is expected that about 110 people will take part in this research study.

Details

Condition	Breast Cancer, Breast Cancer, Breast Cancer - HER2 Positive, Chronic Shoulder Pain, Vaginal Atrophy, PD-L1 Negative
Age	18-100 years
Treatment	Pembrolizumab, Sacituzumab Govitecan
Clinical Study Identifier	NCT04468061
Sponsor	Dana-Farber Cancer Institute
Last Modified on	19 February 2024

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Eligibility		Yes	No	Not Sure
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 measured with standard of care testing
	Participants must be treatment-nave in the metastatic setting
	Participants must have evaluable or measurable disease per RECIST 1.1. See Section 11 for the assessment of measurable disease. 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 (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 in 3.1.13, 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 in 3.1.13
	Prior radiation therapy: Patients may have received prior radiation therapy. Radiation therapy must be completed at least 14 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 in 3.1.13. A 1-week washout is permitted for palliative radiation (2 weeks of radiotherapy) to non-CNS disease
	Stable, previously treated brain metastases are permitted, with the following
	provisions
	Prior WBRT or SBRT should complete 14 days before study treatment initiation. Note: Reimaging at baseline post-treatment is not required, but baseline scans should be after radiation or surgery or within 21 days of randomization
	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
	Note: Criteria must be met without erythropoietin dependency and without packed red blood cells
	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 150 days (5 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 (Appendix B)
	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 7 months after the last dose of study treatment (i.e., 90 days (duration of sperm turnover) plus the time required for the investigational drug to undergo approximately five half- lives, Appendix B)
	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
	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

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Sacituzumab Govitecan +/- Pembrolizumab in Metastatic TNBC