This is a Phase I/II Study to determine the safety and efficacy of Sacituzumab Govitecan and Zimberelimab with stereotactic radiation (SRS) in participants with metastatic triple negative breast cancer with brain metastases, compared to treatment with Sacituzumab Govitecan alone.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
31
Stereotactic Radiation to intact brain metastases or post-operative cavity.
One week +/- 4 days following receipt of SRS, zimberelimab 360 mg IV will be administered. This will be followed by zimberelimab 360 mg IV every 3 weeks.
SG will be administered on days 1 and 8 (10 mg/kg) of 21 day treatment cycles. This will be one week +/- 4 days following receipt of SRS for the first dose.
Moffitt Cancer Center
Tampa, Florida, United States
RECRUITINGPhase I: Neurologic Toxicity
Neurologic Toxicity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v5). A Neurologic Toxicity will be defined as any Grade 3 or higher toxicity that occurs during the Dose Limiting Toxicity evaluation period. Toxicity that is clearly and directly related to the primary disease or to another etiology is excluded from this definition. * Symptomatic radionecrosis, defined by surgical pathology or multidisciplinary evaluation. * Grade ≥ 3 headaches * Grade ≥ 3 memory impairment * New onset grade ≥ 3 seizures
Time frame: Up to 9 Weeks
Phase II: Progression Free Survival (PFS)
Evaluate the PFS of SG and zimberelimab with SRS among patients with metastatic triple negative breast cancer. PFS is time from the date of start of treatment to the investigator-determined date of progression or death due to any cause, whichever occurs first.
Time frame: Up to 12 Months
Phase II: Intracranial Progression Free Survival (PFS)
Time from the date of start of treatment to the investigator-determined date of progression (determined by Response Assessment in Neuro-Oncology (RANO)) or death due to any cause, whichever occurs first. Progression is measured by a ≥ 20% increase in sum longest distance relative to nadir in target lesions and unequivocal or progressive disease in non-target lesions.
Time frame: Up to 12 Months
Phase II: Extracranial Progression Free Survival (PFS)
PFS will be measured from the date of start of treatment to the investigator-determined date of progression (determined by Immune-related Response Evaluation Criterial in Solid Tumors (irRECIST)) or death due to any cause, whichever occurs first. Progression is defined as ≥ 20% increase in tumor burden.
Time frame: Up to 33 Months
Phase II: Overall Survival (OS)
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OS will be measured from the date of start of treatment to death.
Time frame: Up to 33 Months
Phase II: Local Brain Control
Number of participants with Local Brain Control will be determined from irradiated lesions according to RANO criteria.
Time frame: Up to 33 Months
Phase II: Distant Brain Control
Number of participants with Distant Brain Control will be determined by the development of new lesions outside the irradiated area.
Time frame: Up to 33 months