Sacituzumab Govitecan +/- Pembrolizumab in Metastatic TNBC
Saci-IO TNBC: Randomized Phase II Study of Sacituzumab Govitecan With or Without Pembrolizumab in PD-L1-negative Metastatic Triple Negative Breast Cancer (TNBC)
1 other identifier
interventional
110
1 country
15
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)
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2 breast-cancer
Started Jul 2020
Longer than P75 for phase_2 breast-cancer
15 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 8, 2020
CompletedFirst Posted
Study publicly available on registry
July 13, 2020
CompletedStudy Start
First participant enrolled
July 20, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 1, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
April 1, 2029
April 29, 2026
April 1, 2026
6.7 years
July 8, 2020
April 27, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Progression Free Survival (PFS)
Compare PFS of patients randomized to receive sacituzumab govitecan in combination with pembrolizumab (Arm A) versus those randomized to receive sacituzumab govitecan monotherapy (Arm B). Defined as the time from study randomization to disease progression, per RECIST 1.1 or medical judgment, the latter based on established clinical parameters, such as rising tumor markers and physical exam evidence of progression, i.e. worsening chest wall disease, or death due to any cause, whichever occurred first.
3 years
Secondary Outcomes (7)
Overall Survival (OS)
3 years
Objective Response Rate (ORR)
3 years
Duration of response (DOR)
3 years
Time to objective response (TTOR)
3 years
Time to progression (TTP)
3 years
- +2 more secondary outcomes
Study Arms (3)
Sacituzumab Govitecan + Pembrolizumab
EXPERIMENTALParticipants 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.
Sacituzumab Govitecan
EXPERIMENTALParticipants 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
Retreatment
EXPERIMENTALParticipants 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
Intravenous Infusion
Intravenous Infusion
Eligibility Criteria
You may qualify if:
- 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.
- 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:
- +12 more criteria
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Dana-Farber Cancer Institutelead
- Gilead Sciencescollaborator
- Merck Sharp & Dohme LLCcollaborator
Study Sites (15)
Stamford Hospital
Stamford, Connecticut, 06904, United States
Miami Cancer Institute at Baptist Health (Kendall)
Miami, Florida, 33176, United States
Miami Cancer Institute at Baptist Health
Plantation, Florida, 33324, United States
University of Chicago Medical Center
Chicago, Illinois, 60637, United States
Eastern Maine Medical Center
Brewer, Maine, 04412, United States
Dana Farber Cancer Institute
Boston, Massachusetts, 02215, United States
DFCI @ Foxborough
Foxborough, Massachusetts, 02035, United States
DFCI @ Milford Regional Hospital
Milford, Massachusetts, 01757, United States
DF/BWCC in Clinical Affiliation with South Shore Hospital
South Weymouth, Massachusetts, 02190, United States
The University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27599, United States
The Christ Hospital Cancer Center
Cincinnati, Ohio, 45219, United States
Ohio State University Medical Center
Columbus, Ohio, 43212, United States
University of Pennsylvania-Abramson Cancer Center
Philadelphia, Pennsylvania, 19104, United States
Medical University of South Carolina
Charleston, South Carolina, 29425, United States
Sarah Cannon Research Institute
Chattanooga, Tennessee, 37404, United States
Related Publications (1)
Kwapisz D. Sacituzumab Govitecan-hziy in Breast Cancer. Am J Clin Oncol. 2022 Jul 1;45(7):279-285. doi: 10.1097/COC.0000000000000919. Epub 2022 May 12.
PMID: 35728046DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Ana C Garrido-Castro, MD
Dana-Farber Cancer Institute
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
July 8, 2020
First Posted
July 13, 2020
Study Start
July 20, 2020
Primary Completion (Estimated)
April 1, 2027
Study Completion (Estimated)
April 1, 2029
Last Updated
April 29, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF
- Time Frame
- Data can be shared no earlier than 1 year following the date of publication.
- Access Criteria
- Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu
The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.