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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Investigational Drug AI Analysis

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

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Goal: Evaluate safety and preliminary efficacy of combining stereotactic radiosurgery (SRS) with sacituzumab govitecan (SG) and the PD-1 inhibitor zimberelimab versus SG alone in metastatic triple-negative breast cancer (mTNBC) patients with brain metastases.

Patients: Adults ≥18 years with biopsy-proven triple-negative breast cancer (ER/PR ≤10% by IHC) and MRI-confirmed brain metastases, ECOG 0–2, eligible for SRS to intact metastases or postoperative cavities, with measurable intracranial disease per RANO-BM. Prior taxane and anthracycline required. Stable or no steroids (≤8 mg/day dexamethasone) allowed; prior SRS/FSRT permitted if current measurable lesions were not previously irradiated. Key exclusions include leptomeningeal disease, active autoimmune disease requiring systemic therapy, prior pneumonitis/ILD requiring steroids, significant cardiac disease, active infections (including uncontrolled HBV/HCV, HIV with detectable viral load), active IBD, need for supplemental oxygen, pregnancy or breastfeeding, recent major surgery without recovery, recent anticancer therapy without recovery, and prior topoisomerase I inhibitors in the setting of brain metastases.

Design: Phase I/II, non-randomized study assessing safety (dose-limiting neurologic toxicity) followed by efficacy. Allocation is not applicable; comparison to SG alone is planned contextually but not as a randomized parallel arm within this protocol.

Treatments: Experimental regimen: SRS to brain lesions or postoperative bed, followed one week later by sacituzumab govitecan 10 mg/kg IV on days 1 and 8 plus zimberelimab 360 mg IV on day 1 of each 21-day cycle; imaging every 9 weeks. Sacituzumab govitecan is an antibody–drug conjugate targeting Trop-2 linked to the topoisomerase I inhibitor SN-38; it is standard in pretreated mTNBC with demonstrated improvements in response rate and survival versus chemotherapy. Zimberelimab is a fully human IgG4 monoclonal antibody against PD-1 that blocks PD-1/PD-L1/PD-L2 interactions to restore antitumor T-cell activity. Across phase I/II studies in solid tumors and lymphoma, zimberelimab has shown objective responses in the 20–30% range depending on indication with a safety profile consistent with PD-1 inhibitors, including mostly grade 1–2 immune-related toxicities (e.g., hypothyroidism, anemia).

Outcomes: Primary endpoints: Phase I—rate of grade ≥3 neurologic toxicity during the DLT window, including symptomatic radionecrosis, grade ≥3 headaches, memory impairment, or new-onset grade ≥3 seizures; Phase II—progression-free survival (PFS) up to 12 months. Secondary endpoints: intracranial PFS (RANO), extracranial PFS (irRECIST), overall survival, local brain control of irradiated lesions, and distant brain control (new lesions outside irradiated fields), assessed up to 33 months.

Burden on patient: Moderate to high. Patients undergo SRS, IV infusions on days 1 and 8 every 21 days, and zimberelimab on day 1, necessitating frequent clinic visits. Imaging every 9 weeks and neurological assessments add visit time, and close monitoring for immune-related events and SG-related toxicities (e.g., neutropenia, diarrhea) may require additional labs and potential supportive care visits. No noted serial pharmacokinetic blood draws or mandatory biopsies reduce intensity compared with some phase I studies, but the combination of radiation, dual IV therapies, and frequent assessments remains more burdensome than standard single-agent therapy.

Last updated: Oct 2025

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Moffitt Cancer Center

Tampa, Florida, 33612, United States

[email protected] / 813-745-6911

Status: Recruiting

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