Genomic and Transcriptomic Predictors of Sequential SG Sensitivity After T-DXd in ER+/HER2-Low Metastatic Breast Cancer
- Registration Number
- NCT06665178
- Lead Sponsor
- British Columbia Cancer Agency
- Brief Summary
Advanced hormone positive (HR+), HER2 negative breast cancer continues to pose a challenge when patients have progressed on CDK4/6 inhibitor and endocrine therapy leaving limited treatment options. Antibody-drug conjugates (ADCs) such as sacituzumab govitecan (SG) and trastuzumab deruxtecan (T-DXd) have changed practice due to significant improvement in progression free survival (PFS) and overall survival (OS) seen in this disease setting. There is a genuine interest to use SG sequentially after T-DXd, however there is no current prospectively curated evidence to support this strategy. Though the epitope is different, the payload are both topoisomerase I inhibitors. Thus, evidence is needed of both clinical efficacy and identification of mechanisms of sensitivity and resistance to sequential ADCs in HER-2 low MBC.
It is hypothesized that performing whole genome and whole transcriptome sequencing in fresh tumour biopsies post progression of T-DXd and prior to SG in ER+/HER2 low metastatic breast cancer (MBC) will provide mechanistic insights into identifying biomarkers, and thus patients, sensitive to sequential SG.
- Detailed Description
This is a prospective single-centre Canadian study (BC Cancer Vancouver) enrolling ER+/HER2 low MBC with disease progression after at least one line of endocrine therapy in combination with a CDK 4/6 inhibitor and at least one line of chemotherapy which must include T-DXd as the immediate prior line of treatment in the advanced stage setting.
Patients will receive SG at an initial dose of 10 mg per kilogram intravenously on day 1 and 8 of 21 day cycles. Treatment will continue until evidence of progressive disease, significant toxicity in which patient and or physician wishes to discontinue treatment and/or patient or physician desire to discontinue treatment for any reason.
Tumor specimens will collected from biopsies between the time of informed consent and prior to first administration of SG. The pathology will be reviewed and nucleic acids extracted. Constitutional DNA representing normal cells will be extracted from peripheral blood. PCR-free DNA libraries and either strand-specific or ribo-depleted RNA libraries will be constructed. Following which whole genome sequencing and transcriptome sequencing will be performed.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 20
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Sacituzumab Govitecan Sacituzumab Govitecan Patients will receive SG at an initial dose of 10 mg per kilogram intravenously on day 1 and 8 of 21 day cycles.
- Primary Outcome Measures
Name Time Method Altered Tumor Genes by PFS Duration on SG Post T-DXd Up to an average of 6 months Number and identification of altered/mutated genes in the tumors in the subgroup of patients with a longer PFS on SG post T-DXd compared to the tumors in the subgroup of patients with a shorter PFS on SG post T-DXd.
- Secondary Outcome Measures
Name Time Method Grade 2-4 toxicities Up to an average of 3 months Number of Participants with the CTCAE version 5 grade 2-4 toxicities reported in SG post T-DXd in ER+/HER2 low MBC
Trop-2 expression and HER-2 expression Up to an average of 12 months Trop-2 expression and HER-2 expression by IHC in the metastatic biopsy and correlation with PFS and RR
Dose intensity Up to an average of 3 months Dose intensity (with and without growth factor support) of SG delivered post T-DXd in ER+/HER2 low MBC
Progression free survival (PFS) Up to an average of 6 months Progression free survival (PFS) of SG post T-DXd in ER+/HER2 low MBC as measured by RECIST criteria
Response rate (RR) Up to an average of 6 months Response rate (RR) of SG post T-DXd as measured by RECIST 1.1 criteria
Overall survival Up to an average of 12 months Overall survival of SG post T-DXd
Trial Locations
- Locations (1)
BC Cancer - Vancouver Center
🇨🇦Vancouver, British Columbia, Canada