Phase I/II Study of Stereotactic Radiation and Sacituzumab Govitecan With Zimberelimab in the Management of Metastatic Triple Negative Breast Cancer With Brain Metastases (TARGET-TNBC)

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Active drug More information Moderate burden on patient More information

Trial Details

Sponsor: H. Lee Moffitt Cancer Center and Research Institute (other)

Phase: 1/2

Start date: Dec. 19, 2024

Planned enrollment: 31

Trial ID: NCT06238921
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More trial details at ClinicalTrials.gov More info

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chevron Show for: Zimberelimab (WBP-3055, GLS-010, AB122)

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Goal: To evaluate the safety and efficacy of sacituzumab govitecan and zimberelimab in combination with stereotactic radiosurgery (SRS) for patients with metastatic triple-negative breast cancer (TNBC) with brain metastases, compared to sacituzumab govitecan alone.

Patients: Adult patients (≥18 years) with metastatic triple-negative breast cancer and measurable brain metastases, ECOG 0-2, who are eligible for SRS. Patients may have prior taxane and anthracycline treatment and prior SRS/FSRT if lesions included in the trial have not previously been irradiated. Excludes those with leptomeningeal disease, significant uncontrolled comorbidities, active autoimmune disease requiring immunosuppressive therapy, and prior topoisomerase I inhibitor exposure for brain metastases.

Design: Single-arm, open-label, non-randomized phase I/II trial with a dose-escalation (safety) phase followed by an expansion (efficacy) phase. All patients receive the experimental combination therapy. Participants are closely monitored for toxicity, response, and progression.

Treatments: All patients receive stereotactic radiosurgery to brain metastases, followed by sacituzumab govitecan (10mg/kg IV on days 1 and 8 of a 21-day cycle) and zimberelimab (360 mg IV on day 1 every 3 weeks). Zimberelimab is a fully human anti-PD-1 monoclonal antibody that blocks PD-1/PD-L1 interaction, reactivating anti-tumor immune responses. In prior trials for cervical cancer and other tumors, zimberelimab has demonstrated objective response rates in the 20–28% range and a safety profile consistent with other PD-1 inhibitors, the most common adverse events being grade 1-2 hypothyroidism and anemia. Sacituzumab govitecan is an antibody-drug conjugate targeting Trop-2, already approved for metastatic TNBC.

Outcomes: Primary endpoints include safety (phase I: neurologic toxicity graded by CTCAE v5, focusing on grade 3 or higher events) and progression-free survival (PFS, phase II). Secondary outcomes are intracranial and extracranial PFS, overall survival (OS), local and distant brain control, all tracked up to 33 months. Neurologic adverse events of interest include symptomatic radionecrosis, grade ≥3 headache, memory impairment, and new-onset seizures.

Burden on patient: Patients will undergo SRS, receive intravenous therapies every three weeks, and have follow-up with brain imaging at nine-week intervals. Standard laboratory monitoring and clinical assessments will be required, and neurologic assessments will be emphasized early in the trial. There is no mention of extra mandatory biopsies or intensive pharmacokinetic blood draws, but patients will require regular visits for imaging and infusion therapy. The overall burden is moderate, similar to other early-phase combination trials for brain metastases, primarily due to the need for frequent clinical, imaging, and neurologic monitoring.

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Moffitt Cancer Center

Tampa, Florida, 33612, United States

[email protected] / 813-745-6911

Status: Recruiting

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