HER2-positive Metastatic Breast Cancer
Conditions
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.
Interventions
DIAGNOSTIC_TESTCE-10-IVD
Leftover tumor tissue from a routine biopsy will be sent for analysis.
Sponsors
Abramson Cancer Center at Penn Medicine
Translational Breast Cancer Research Consortium
Danaher Inc.
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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." |
| 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 |
Countries
United States
Contacts
CONTACTAngela DeMichele, MD
PRINCIPAL_INVESTIGATORAngela DeMichele, MD
Abramson Cancer Center at Penn Medicine
Outcome results
None listed