Evaluating sacituzumab govitecan for localized triple negative breast cancer

A Phase 2 Study of Response-guided Neoadjuvant Sacituzumab Govitecan (IMMU-132) in Patients With Localized Triple-Negative Breast Cancer (NeoSTAR)

This study is testing a new drug called sacituzumab govitecan for people with localized triple negative breast cancer to see if it can help them.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 260 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Massachusetts General Hospital (Academic / other)
• Drugs / interventions: sacituzumab, Pembrolizumab, chemotherapy, immunotherapy
• Locations: 5 sites (Boston, Massachusetts and 4 other locations)
• Trial ID: NCT04230109 on ClinicalTrials.gov

What this trial studies

This Phase II clinical trial is designed to assess the safety and effectiveness of sacituzumab govitecan in patients with localized triple negative breast cancer (TNBC). The study includes an initial cohort receiving sacituzumab govitecan alone, followed by a cohort that will receive a combination of sacituzumab govitecan and pembrolizumab. Participants will undergo screening for eligibility and receive treatment for up to 12 weeks, with follow-up evaluations. The trial aims to explore the potential of this investigational drug in treating a specific subset of breast cancer patients.

Who should consider this trial

Good fit: Ideal candidates are adults with histologically confirmed invasive breast cancer that is ER-negative, PR-negative, and HER2-negative.

Not a fit: Patients with metastatic breast cancer or those whose tumors are ER-positive, PR-positive, or HER2-positive may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with localized triple negative breast cancer.

How similar studies have performed: Other studies have shown promise with similar antibody-drug conjugate approaches, indicating potential for success in this area.

Eligibility criteria

Inclusion Criteria:

* Female or male patients ≥ 18 years of age.
* Histologically confirmed diagnosis of invasive breast cancer, previously untreated.
* Participants must have biopsy proven ER negative (ER-), PR negative (PR-), HER2 negative (HER2-), invasive breast cancer. ER, PR, and HER2 positivity would be determined per ASCO/CAP guidelines by institutional (local) assessment. Patients with multi-focal and multicentric disease are eligible provided all histologically examined lesions are ER-/PR-/HER2- (local assessment). The need to biopsy additional lesions is at the discretion of the treating physician. Patients with bilateral invasive breast cancer are eligible provided all histologically examined lesions are ER-/PR-/HER2- (local assessment).
* Primary tumor (at least one lesion) 1 cm or greater measured by radiological imaging. Regional lymph node AJCC (v7) TNM stages N0-N2. If node positive, any primary tumor size is permissible. Absence of distant metastatic disease (AJCC TNM stage M0). Staging scans are not required and are per discretion of the treating physician.
* Pre- and postmenopausal women are eligible.
* ECOG performance status = 0, 1 (Karnofsky ≥60%, see Appendix A)
* Ability to understand and the willingness to sign a written informed consent form (ICF). Patient has signed the ICF prior to any screening procedures being performed and is able to comply with protocol requirements, including research biopsy.
* Patient has adequate bone marrow and organ function as defined by the following laboratory values at screening:
* Absolute neutrophil count (ANC) ≥ 1,500 per mm3
* Platelets ≥ 100,000 per mm3
* Hemoglobin ≥9.0 g/dL
* INR ≤1.5
* Serum creatinine \<1.5 mg/dL or creatinine clearance ≥50 mL/min
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \<2.5 x ULN.
* Total bilirubin ≤1.5 x ULN or in patients with well-documented Gilbert's Syndrome direct bilirubin ≤1.5 x ULN.

Exclusion Criteria:

* Inflammatory breast cancer, or locally recurrent breast cancer
* Participants currently receiving systemic therapy for any other malignancy or having received systemic therapy for a malignancy in the preceding 3 years.
* Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia,or psychiatric illness/social situations that would limit compliance with study requirements.
* Clinically significant, uncontrolled heart disease and/or cardiac reppolarization abnormality including any of the following:

  * History of angina pectoris, symptomatic pericarditis, coronary artery bypass graft (CABG) or myocardial infarction within 6 months prior to study entry.
  * History of cardiac failure, known cardiomyopathy (LVEF \< 50%; new LVEF assessment is not specifically required for this trial), significant/symptomatic bradycardia, Long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome or any of the following:
* Known risk to prolong the QT interval or induce Torsade's de Pointes.
* Uncorrected hypomagnesemia or hypokalemia.
* Systolic Blood Pressure (SBP) \>160 mmHg or \<90 mmHg.
* Bradycardia (heart rate \<50 at rest), by ECG or pulse. On screening, inability to determine the QTcF interval on the ECG (i.e.: unreadable or not interpretable) or QTcF \>470 screening ECG
* Pregnant or breast-feeding women are excluded from this study because the safety of study medications is not established.
* Known HIV-positive participants on combination antiretroviral therapy are ineligible.
* These participants are at increased risk of lethal infections when treated with marrow-suppressive therapy. Separate HIV testing for this trial is not required. Similarly, separate Hepatitis B or C testing for this trial is not required, but patients with known (or history) of hepatitis B positive, or hepatitis C positive infection will be excluded

Where this trial is running

Boston, Massachusetts and 4 other locations

• Beth Israel Deaconess Medical Center — Boston, Massachusetts, United States (Recruiting)
• Dana Farber Cancer Institute — Boston, Massachusetts, United States (Recruiting)
• Massachusetts General Hospital — Boston, Massachusetts, United States (Recruiting)
• Massachusetts General Hospital - North Shore Cancer Center — Danvers, Massachusetts, United States (Recruiting)
• Massachusetts General Hospital at Newton-Wellesley Hospital — Newton, Massachusetts, United States (Recruiting)

Study contacts

• Principal investigator: Laura Spring, MD — Massachusetts General Hospital
• Study coordinator: Laura Spring, MD

Conditions Invasive Breast Cancer; Triple Negative Breast Cancer; ER-Negative Breast Cancer; PR-Negative Breast Cancer; HER2-negative Breast Cancer