Trial in Progress: BRIDGET Trial of Tucatinib Plus Trastuzumab/Pertuzumab or Trastuzumab Emtansine After Isolated Intracranial Progression in HER2+ MBC

In the setting of a first isolated brain relapse, current treatment guidelines recommend continuing current systemic therapy. The standard of care for first-line therapy of advanced HER2+ metastatic breast cancer (MBC) is trastuzumab and pertuzumab plus taxane; however, brain permeability is poor with this regimen. Tucatinib is a brain-penetrable HER2-targeting tyrosine kinase inhibitor that has demonstrated improvement in intracranial progression-free survival (PFS) and overall survival (OS) when added to trastuzumab and capecitabine in patients with stable or active HER2+ brain metastasis. Therefore, it is hypothesized that the addition of tucatinib to trastuzumab/pertuzumab (TP) or trastuzumab emtansine (T-DM1) may delay or prevent secondary brain metastases in patients with HER2+ MBC with isolated brain relapse or progression.

The BRIDGET (NCT05323955) trial is a single-arm, phase 2, multicenter study that is evaluating the addition of tucatinib to TP or T-DM1 after local therapy in patients with isolated brain relapse or progression. The study will enroll patients with advanced HER+ breast cancer who are currently receiving standard-of-care treatment with TP or T-DM1 in the metastatic setting, or adjuvant trastuzumab-based or T-DM1 therapy with isolated brain recurrence, and absence or stable extracranial disease per RECIST version 1.1. Patients with leptomeningeal disease or untreated brain lesions ≥5 mm will be excluded. Eligible patients will be enrolled after first or second brain metastasis relapse or progression within 8 weeks of local therapy with stereotactic radiosurgery with or without surgical resection and receive tucatinib in addition to current therapy of TP or T-DM1.

The primary endpoint is intracranial PFS compared with a historical control (H0, PFS <5 months; HA, iPFS >8 months); secondary end points include PFS by RECIST version 1.1, PFS of extracranial disease, locally treated versus new distant intracranial metastasis PFS, site of first progression (brain vs non-brain), OS, and toxicity in patients with brain metastasis. To conduct correlative studies, samples including archival tissue, cerebrospinal fluid (optional), whole blood for ctDNA will be collected. Patient-reported outcomes will be collected.

A total of 48 patients are planned to be enrolled at 9 US sites as part of the Hoosier Cancer Research Network. As of November 16, 2023, 10 patients have been recruited across the 7 sites that are currently open.

Source:

Sammons S, Van Swearingen A, Noteware L, et al. Secondary BRain metastases prevention after Isolated intracranial progression on trastuzumab/pertuzumab or T-DM1 in patients with aDvanced human epidermal Growth factor receptor 2+ brEast cancer with addition of Tucatinib. Presented at the 46th San Antonio Breast Cancer Symposium Annual Meeting, December 5-9, 2023; San Antonio, TX: Abstract PO5-20-02.