QuantifyHER: Quantitative Immunofluorescence and/or RT-qPCR for Measuring HER2 in HER2-low Metastatic Breast Cancer

Recruiting

• Conditions: HER2-positive Metastatic Breast Cancer

• Registration Number: NCT06551116
• Lead Sponsor: Abramson Cancer Center at Penn Medicine

Brief Summary

This study will assess whether a quantitative, HER2 assay can accurately and reliably discriminate between responders and non-responders among patients with HER2 IHCI+ metastatic breast cancer who are receiving T-Dxd.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-07-29
• Study First Submitted QC: 2024-08-09
• Study First Posted: 2024-08-13
• Study Start: 2024-10-10
• Status Verified: 2025-05
• Last Update Submitted: 2025-09-03
• Last Update Posted: 2025-09-05
• Primary Completion: 2029-09-01
• Study Completion: 2029-09-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

• Women and men age > 18 years
• Metastatic breast cancer, histologically- confirmed. Any estrogen receptor (ER) status is allowed. ER status will be determined by local laboratory assessment utilizing ASCO/CAP guidelines.
• Primary and/or metastatic tumor with 1+ level of expression of HER2 by immunohistochemistry as determined by local laboratory assessment utilizing ASCO/CAP guidelines.
• Measurable disease by cross-sectional imaging at the start of treatment. Patients with measurable bone-only disease or active brain metastases are eligible.
• Archival tissue available for biomarker assessment. One specimen should be the most recent metastatic biopsy. If HER2 1+ status was determined on a different specimen (either primary or metastatic tissue), that specimen is also required. Samples obtained from bone metastases that were processed via decalcification methods are not eligible.
• Intention to initiate therapy with T-DXd (Enhertu) at FDA-approved dose and schedule as next line of therapy. If T-DXd was already initiated, patients must be registered within 30 days of initiation.
• Ability to provide informed consent

Exclusion Criteria

• Concurrent Her2-overexpressing metastatic breast cancer (as confirmed by a metastatic biopsy with IHC 3+ or IHC 2+ with FISH amplified as per standard ASCO/CAP guidelines)

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Real-World Objective Response Rate	from date of first dose of T-DXd to date of last dose of T-DXd for each. Up to 100 months	Association between quantitative HER2 expression (as a continuous variable) and real-world objective response rate

Secondary Outcome Measures

Name	Time	Method
Association between combined mRNA + QIF and real-world Objective Response Rate	from date of first dose of T-DXd to date of last dose of T-DXd for each. Up to 100 months	Comparison, based on rwORR, of a linear combination of HER2 QIF and mRNA, versus either alone in ability to discriminate T-DXd responders from non- responders
Real-World Progression Free Survival	from date of first dose of T-DXd to date of last dose of T-DXd for each.Up to 100 months	Association between quantitative HER2 expression (as a continuous variable) and real world Progression Free Survival
Threshold for HER2 QIF and/or mRNA levels	from date of first dose of T-DXd to date of last dose of T-DXd for each. Up to 100 months	cut-off value for HER2 QIF, mRNA and the combination below which patients will not respond to T-DXd."
Real-World Progression Free Survival and Objective Response Rate by estrogen receptor expression	from date of first dose of T-DXd to date of last dose of T-DXd for each. Up to 100 months	Association between HER2 expression by quantitative immunofluorescence and mRNA in HER2 IHC 1+ tumors and both rwORR and rwPFS, stratified by mRNA ER expression

Trial Locations

Locations (30)

University of California San Francisco Medical Center; 🇺🇸 San Francisco, California, United States

Montefiore Einstein Medical Center; 🇺🇸 The Bronx, New York, United States

Smilow Cancer Hospital-Derby Care Center; 🇺🇸 Derby, Connecticut, United States

Smilow Cancer Hospital Care Center; 🇺🇸 Westerly, Rhode Island, United States

Smilow Cancer Hospital at Glastonbury; 🇺🇸 Glastonbury, Connecticut, United States

Smilow Cancer Hospital Care Center at Greenwich; 🇺🇸 Greenwich, Connecticut, United States

Smilow Cancer Hospital at Saint Francis; 🇺🇸 Hartford, Connecticut, United States

Yale-New Haven Hospital North Haven Medical Center; 🇺🇸 New Haven, Connecticut, United States

Yale Cancer Center; 🇺🇸 New Haven, Connecticut, United States

Smilow Cancer Hospital Care Center at Long Ridge; 🇺🇸 Stamford, Connecticut, United States

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