Clinical trial NCT04230109: Sacituzumab Govitecan In TNBC
Official title: A Phase 2 Study of Response-guided Neoadjuvant Sacituzumab Govitecan (IMMU-132) in Patients With Localized Triple-Negative Breast Cancer (NeoSTAR)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Invasive Breast Cancer
Triple Negative Breast Cancer
ER-Negative Breast Cancer
PR-Negative Breast Cancer
HER2-negative Breast Cancer
Keywords: Invasive Breast Cancer
Triple Negative Breast Cancer
ER-Negative Breast Cancer
PR-Negative Breast Cancer
HER2-negative Breast Cancer
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: Gilead Sciences
First posted: 2020-01-18
Enrollment: 260
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This research study is studying to evaluate sacituzumab govitecan for individuals with localized triple negative breast cancer (TNBC)

The names of the study drugs involved in this study is:

* Sacituzumab govitecan (SG)
* Pembrolizumab (combination therapy with SG)

Detailed description: This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. "Investigational" means that the drug is being studied.

This research study involves an experimental study treatment. The names of the study drugs involved in this study is:

* Sacituzumab govitecan (SG)
* Pembrolizumab (combination therapy with SG)

The study is a umbrella study multi-arm phase II study of neoadjuvant SG-based therapy in patients with localized BC. The first cohort involves SG monotherapy. After the monotherapy cohort completes enrollment, the combination therapy cohort (SG with pembrolizumab) for patients with localized BC will open.

Future planned arms include SG with/without pembrolizumab for patients with Hormone Receptor positive (HR+) breast cancer and inflammatory breast cancer (IBC).

The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits.

* Eligible participants will receive Sacituzumab govitecan for up to 12 weeks.
* This can be followed by standard chemotherapy at the discretion of the treating physician.
* It is expected that about 50 people will take part in this research study.

The U.S. Food and Drug Administration (FDA) has not approved Sacituzumab govitecan as a treatment for patients with metastatic TNBC.

Sacituzumab govitecan (SG) is an antibody-drug conjugate which means it's made up of an antibody attached to an anticancer drug. An antibody is a protein normally made the immune system. Sacituzumab govitecan is believed to work by binding the antibody portion of the drug in the tumor(s) while the anticancer drug portion works to prevent cancer cells from growing/spreading.

After the SG monotherapy cohort completes enrollment, the combination therapy cohort (SG with immunotherapy) will open.

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

Primary outcomes:
measure: Pathological complete response(pCR) rate with sacituzumab govitecan
timeFrame: 12 Weeks
Secondary outcomes:
measure: Disease-Free Survival
timeFrame: Time from the first dose of study treatment to disease recurrence/progression by RECIST v1.1 or death due to any cause, up to 36 months
measure: Overall Survival
timeFrame: defined as the time from the first dose of study treatment to the date of death or last contact up to 36 months
measure: Change in Breast Conserving Surgery Rate (BCS) rate
timeFrame: 12 Weeks
measure: Number of Participants with Treatment Related Adverse Events as Assessed by CTCAE v5.0
timeFrame: Baseline to 12 weeks
measure: Assessment of Quality of life (QOL)
timeFrame: Baseline up to 12 Weeks
Other outcomes:
Locations:
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Danvers
country: United States
facility: Massachusetts General Hospital - North Shore Cancer Center
state: Massachusetts
city: Newton
country: United States
facility: Massachusetts General Hospital at Newton-Wellesley Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Laura Spring, MD
role: PRINCIPAL_INVESTIGATOR
References: