A Randomized, Open-label, Phase 3 Study of Adjuvant Sacituzumab Govitecan and Pembrolizumab Versus Treatment of Physician's Choice in Patients With Triple Negative Breast Cancer Who Have Residual Invasive Disease After Surgery and Neoadjuvant Therapy

The purpose of this study is to see if sacituzumab govitecan in combination with pembrolizumab can improve outcomes and delay the return of disease in participants with high-risk early triple-negative breast cancer (TNBC) when compared to pembrolizumab alone or pembrolizumab in combination with capecitabine.  

For more information, please visit https://clinicaltrials.gov/search?term=NCT05633654

Inova Schar Cancer
8081 Innovation Park Drive
Fairfax, VA 22031

Inova Fair Oaks Hospital
3580 Joseph Siewick Drive
Fairfax, VA 22033

Inova Fairfax Medical Center
3300 Gallows Road
Falls Church, VA 22042

• Patients must be 18 years of age or older, able to understand and give written informed consent
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
• Patients must have had adequate excision and surgical removal of all clinical evidence of disease in the breast and/or lymph nodes as well as radiotherapy as indicated in the eligibility criteria prior to screening.
• Triple negative breast cancer status must be confirmed per current American Society of Clinical Oncology and College of American Pathologists (ASCO/CAP) guidelines.
• Estrogen receptor (ER) and progesterone receptor (PgR) expression must be < 10%.
• Patients must have a history of clinical stage T1, N1-2 or T2-4, N0-2 and histologically confirmed TNBC as determined by the investigator with residual invasive disease in the breast or lymph node(s) after completion of neoadjuvant therapy and surgery. Additionally, the presence of distant metastatic disease must be ruled out.

• Stage IV (metastatic) breast cancer
• Prior neoadjuvant HER2-directed therapy; prior or current endocrine therapy
• History of any prior (ipsi- or contralateral) invasive breast cancer. Note: Prior DCIS is allowed.
• Patients with germline BRCA mutations
• Evidence of recurrent disease (locoregional and/or distant relapse) following preoperative therapy and surgery
• Patients may not be participating in a study with an investigational agent or investigational device within 4 weeks prior to randomization. Patients participating in observational studies are eligible.
• History of other malignancy within the last 5 years except for appropriately treated carcinoma in situ of the cervix, nonmelanoma skin carcinoma, Stage I uterine cancer, or other nonbreast malignancies with an outcome similar to those mentioned above
• Patients who need radiotherapy treatment but are contraindicated due to medical reasons (eg, connective tissue disorder or prior ipsilateral breast radiation)
• Inadequate cardiac function postoperatively, ie, screening LVEF < 50% on ECHO or MUGA
• Have previously received topoisomerase 1 inhibitors or antibody-drug conjugates (ADCs) containing a topoisomerase inhibitor
• Major surgical procedure unrelated to breast cancer or significant traumatic injury within approximately 28 days prior to randomization or anticipation of the need for major surgery during the course of study treatment
• Positive serum pregnancy test or women who are breastfeeding
• Known or severe (Grade 3 or higher) hypersensitivity or allergy to SG, or pembrolizumab, their metabolites, or formulation excipient
• Have received prior therapy with an agent directed to another stimulatory or coinhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137)
• Met any of the following criteria for cardiac disease:
  • Myocardial infarction or unstable angina pectoris within 6 months of enrollment.
  • History of serious ventricular arrhythmia (ie, ventricular tachycardia or ventricular fibrillation), high-grade atrioventricular block, or other cardiac arrhythmias requiring antiarrhythmic medications (except for atrial fibrillation that is well controlled with antiarrhythmic medication); history of QT interval prolongation
  • New York Heart Association (NYHA) Class III or greater congestive heart failure
• Have active chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease) or gastrointestinal perforation within 6 months of enrollment
• Patients positive for HIV-1 or 2 with a history of Kaposi sarcoma and/or Multicentric Castleman Disease
• Have active hepatitis B virus (HBV) or hepatitis C virus (HCV). In patients with a history of HBV or HCV, patients with detectable viral loads will be excluded.
• Have undergone an allogenic tissue or solid organ transplant
• Concurrent serious uncontrolled infections requiring treatment
• Has a diagnosis of immunodeficiency or receiving systemic corticosteroid therapy (higher than physiologic doses) ≥ 10 mg of prednisone per day or equivalent or any other form of immunosuppressive therapy within 14 days prior to Cycle 1 Day 1.
• Has received a live or live-attenuated vaccine within 30 days prior to randomization. Administration of killed vaccines are allowed.
• Has an active autoimmune disease that has required systemic treatment in the past 2 years (eg, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
• Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
• Have other concurrent medical or psychiatric conditions that, in the investigator's opinion, may be likely to confound study interpretation or prevent completion of study procedures and follow-up examinations.
• If required per local guidelines, any patient with a blood uracil level ≥ 150 ng/mL is excluded from receiving capecitabine in combination with pembrolizumab as TPC. If required per local guidelines, patients with known dihydropyrimidine dehydrogenase deficiency (by genotyping) are also excluded from receiving capecitabine and do not need to have blood uracil levels assessed at screening.
• For patients intended to be treated with capecitabine, have received any recent or concomitant treatment with brivudine.