Whole Genome and Transcriptome Tumor Sequencing to Identify Predictors of Sensitivity to Sequential Sacituzumab Govitecan (SG) Following Trastuzumab Deruxtecan (T-DXd) Treatment in ER+/HER-2 Low Metastatic Breast Cancer
Overview
- Phase
- Phase 2
- Intervention
- Sacituzumab Govitecan
- Conditions
- Breast Cancer
- Sponsor
- British Columbia Cancer Agency
- Enrollment
- 20
- Locations
- 1
- Primary Endpoint
- Altered Tumor Genes by PFS Duration on SG Post T-DXd
- Status
- Recruiting
- Last Updated
- 10 months ago
Overview
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.
Investigators
Stephen Chia
Medical Oncologist, BC Cancer
British Columbia Cancer Agency
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
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.
Intervention: Sacituzumab Govitecan
Outcomes
Primary Outcomes
Altered Tumor Genes by PFS Duration on SG Post T-DXd
Time Frame: 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 Outcomes
- Grade 2-4 toxicities(Up to an average of 3 months)
- Trop-2 expression and HER-2 expression(Up to an average of 12 months)
- Dose intensity(Up to an average of 3 months)
- Progression free survival (PFS)(Up to an average of 6 months)
- Response rate (RR)(Up to an average of 6 months)
- Overall survival(Up to an average of 12 months)