NCT06595563

HER2 Molecular Imaging With 89Zr-trastuzumab PET/CT as a Predictive Biomarker for Antibody-drug Conjugate Sequencing in Patients With Advanced HER2-positive Breast Cancer

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 87 (estimated)
• Sponsor: Jules Bordet Institute · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

ZEPHIR-02 is a multicentre, open-label phase II study that will enroll subjects with HER2-positive advanced/metastatic breast cancer (mBC) who have experienced disease progression under trastuzumab deruxtecan (T-DXd) in the metastatic setting. All subjects will undergo baseline biopsy, blood collection, FDG-PET/CT and 89Zr-trastuzumab PET/CT (HER2-PET/CT) and will be classified as HER2-PET/CT positive or negative, as previously described in the ZEPHIR trial. Focusing on a central visual "patient-based" classification that captures the entire disease burden, a side-by-side display will be used, comparing baseline FDG-PET/CT (which identifies all FDG-positive metastases regardless of their HER2-imaging status) and HER2-PET/CT. Subjects will be categorized into two HER2-PET/CT patterns (positive vs. negative) based on proportion of FDG-avid tumor load with significant 89Zr-trastuzumab uptake. Subjects classified as "positive" will receive T-DM1 as monotherapy, IV 3.6mg/kg every 3 weeks (21 days +- 3 days) until disease progression, unacceptable toxicity or request of the subject to withdraw from the study. FDG-PET/CT will be performed before cycle 2 of T-DM1 will serve as a research tool to correlate metabolic changes with clinical outcomes. Other FDG-PET/CT will be performed before cycle 4 of T-DM1 for assessment of response. Subjects who demonstrate a partial or complete response (responders) will continue treatment with T-DM1. Subjects who exhibit stable disease or disease progression (non-responders) will discontinue study treatment and enter the survival follow-up period. For responders, subsequent metabolic evaluations will be performed every 3 months, with FDG-PET/CT. Treatment response will be assessed according to metabolic response. For these subjects, mandatory blood samples will be obtained at all metabolic reassessments. Subjects with HER2-PET/CT classified as "negative" will receive treatment of physician's choice (TPC) as per the best local clinical practice and be out of the study. All enrolled subjects will undergo a mandatory biopsy during the pre-treatment period. The study also includes mandatory translational procedures (i.e. collection of tumour biopsy during pre-treatment period and blood samples at pre-specified time points) for exploratory molecular analyses.

Detailed description

ZEPHIR-02 is a multicentre, open-label phase II study that will enroll subjects with HER2-positive advanced/metastatic breast cancer (mBC) who have experienced disease progression under trastuzumab deruxtecan (T-DXd) in the metastatic setting. All subjects will undergo baseline biopsy, blood collection, FDG-PET/CT and 89Zr-trastuzumab PET/CT (HER2-PET/CT) and will be classified as HER2-PET/CT positive or negative, as previously described in the ZEPHIR trial. Focusing on a central visual "patient-based" classification that captures the entire disease burden, a side-by-side display will be used, comparing baseline FDG-PET/CT (which identifies all FDG-positive metastases regardless of their HER2-imaging status) and HER2-PET/CT. Subjects will be categorized into two HER2-PET/CT patterns (positive vs. negative) based on proportion of FDG-avid tumour load with significant 89Zr-trastuzumab uptake. Lesion uptake will be considered significant/pertinent if it is visually higher than the local background. * HER2-PET/CT positive pattern: The entire or majority of the tumour load shows significant tracer uptake. * HER2-PET/CT negative pattern: The dominant part or all of the tumour load lacks significant tracer uptake. Subjects classified as "positive" will receive T-DM1 as monotherapy, IV 3.6mg/kg every 3 weeks (21 days +- 3 days) until disease progression, unacceptable toxicity or request of the subject to withdraw from the study. FDG-PET/CT will be performed before cycle 2 of T-DM1 for early assessment of response and then again before cycle 4. At the early FDG-PET/CT assessment (before cycle 2), response assessment will be done using a cut-off of 15% based on the CONSIST criteria. Subjects who demonstrate a partial or complete response (responders) and will continue treatment with T-DM1. Subjects who exhibit stable disease or disease progression (non-responders) will discontinue study treatment and enter the survival follow-up period. For responders, subsequent metabolic evaluations will be performed every 3 months, with FDG-PET/CT. Treatment response will be assessed according to metabolic response. For these subjects, blood samples will be obtained at all metabolic reassessments (mandatory). The subjects with HER2 PET/CT classified as "negative" will receive treatment of physician's choice (TPC) as per the best local clinical practice. Subsequent treatment will be collected and the subject will enter survival follow-up. All enrolled subjects will undergo a mandatory biopsy during the pre-treatment period. Of note, results of DNA sequencing on the biopsy will be communicated to the treating oncologist, to potentially inform post progression therapy.

Conditions

• HER2-positive Metastatic Breast Cancer
• HER2-positive Advanced Breast Cancer

Interventions

Type	Name	Description
DRUG	Trastuzumab emtansine	T-DM1 will be administered IV at a dose of 3.6 mg/kg every 3 weeks. (21 days +/- 3 days) until disease progression, unacceptable toxicity or request of the subject to withdraw from the study. The total dose will depend on the subject's weight on day 1 of each T-DM1 cycle.

Timeline

• Start date: 2026-02-01
• Primary completion: 2028-03-01
• Completion: 2029-09-01
• First posted: 2024-09-19
• Last updated: 2026-02-19

Locations

1 site across 1 country: Belgium