Sacituzumab Govitecan In TNBC (NeoSTAR)

Mass General Brigham

Status and phase: Enrolling; Phase 2

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

Treatments: Drug: Sacituzumab Govitecan; Drug: Pembrolizumab

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT04230109

19-578

Details and patient eligibility

About

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)

Full 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.

Enrollment: 239 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Female or male patients ≥ 18 years of age.

• Histologically confirmed diagnosis of invasive breast cancer, previously untreated.

• Pre-and postmenopausal women are eligible to participate if not pregnant, not breastfeeding, and at least one of the following conditions applies:

  • Not a woman of childbearing potential (WOCBP) OR

  • A WOCBP who agrees to use effective contraceptive measures that have a failure rate of less than 1% per year from the initiation of treatment through at least 6 months b. after the last dose of study treatment. WOCBP must agree to 1 of the following contraceptive methods:

    • Complete abstinence from intercourse of reproductive potential, or

    • Consistent and correct use of 1 of the following methods of birth control:

      • Nonhormonal intrauterine device (IUD); Hormonal IUD in conjunction with a barrier method; Female sterilization (have had surgical bilateral oophorectomy with or; without hysterectomy), total hysterectomy, or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment; Vasectomy in the male partner (upon medical assessment of surgical success)

• Male patients with female partners of childbearing potential must practice

  • Complete abstinence from intercourse of reproductive potential
  • Have a surgically successful vasectomy upon medical assessment, or
  • Use condoms plus partner use of a contraceptive method with a failure rate of <1% per year during treatment and until 3 months after last dose of study drug.

• 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
  • PT-INR ≤1.5 x institutional ULN unless participant is receiving anticoagulant therapy as long as PT or aPPT is within therapeutic range of intended use of anticoagulants (for patients receiving pembrolizumab only).
  • Serum creatinine <1.5 mg/dL or creatinine clearance ≥50 mL/min (via the Cockcroft-Gault formula) for participants with creatinine levels above institutional upper limit of normal (ULN)
  • Adequate hepatic function (bilirubin ≤ 1.5 ULN, AST and ALT ≤ 2.5 X ULN and serum albumin > 3 g/dL).

Exclusion criteria

• Participants currently receiving systemic therapy for any malignancy or having received systemic therapy for a malignancy in the preceding 3 years. (Concurrent endocrine therapy allowed in the adjuvant setting. Concurrent GnRH agonists allowed in any setting. Concurrent CDK4/6 inhibitor not allowed in any setting.)

• 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 repolarization 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. Higher blood pressure is permissible per discretion of treating physician; 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.

• HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months prior to enrollment are eligible for this trial. Participants who are HBsAg positive are eligible if they have received HBV antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to registration. Participants should remain on anti-viral therapy throughout study intervention and follow local guidelines for HBV anti-viral therapy post completion of study intervention. Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.

• Participants who are not good candidates for the study (as per investigator judgement)

• History of hypersensitivity reactions attributed to compounds of similar chemical or biologic composition to sacituzumab govitecan.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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239 participants in 2 patient groups

Sacituzumab Govitecan (monotherapy cohort)

Experimental group

Description:

\- The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits. * Sacituzumab govitecan via iv, predetermined dosage per protocol, IV, 2 days per each 21-day cycle, for 4 cycles. * This can be followed by standard chemotherapy at the discretion of treating physician.

Treatment:

Drug: Sacituzumab Govitecan

Sacituzumab Govitecan and Pembrolizumab (combination cohort)

Experimental group

Description:

\- The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits. * Sacituzumab govitecan via iv, predetermined dosage per protocol, IV, 2 days per each 21-day cycle, for 4 cycles. * Pembrolizumab via iv, predetermined dosage per protocol, IV, 1 day per each 21-day cycle, for 4 cycles. * This can be followed by standard chemotherapy at the discretion of treating physician.

Treatment:

Drug: Pembrolizumab

Drug: Sacituzumab Govitecan