Actively Recruiting

Phase 2
Age: 18Years +
All Genders
NCT06665178

Genomic and Transcriptomic Predictors of Sequential SG Sensitivity After T-DXd in ER+/HER2-Low Metastatic Breast Cancer

Led by British Columbia Cancer Agency · Updated on 2025-06-25

20

Participants Needed

1

Research Sites

191 weeks

Total Duration

On this page

Sponsors

B

British Columbia Cancer Agency

Lead Sponsor

G

Gilead Sciences

Collaborating Sponsor

AI-Summary

What this Trial Is About

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.

CONDITIONS

Official Title

Genomic and Transcriptomic Predictors of Sequential SG Sensitivity After T-DXd in ER+/HER2-Low Metastatic Breast Cancer

Who Can Participate

Age: 18Years +
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Willing and able to provide signed informed consent approved by UBC/BC Cancer REB
  • Female or male patients 18 years or older at the time of consent
  • Locally advanced or metastatic ER+/HER2 low breast cancer (IHC 1+ or 2+ with FISH or CISH negative as per ASCO/CAP guidelines) including inoperable locally advanced cases treated with palliative intent
  • Prior endocrine therapy with CDK4/6 inhibitor in metastatic setting
  • Prior chemotherapy including trastuzumab deruxtecan (T-DXd) as the immediate prior line before study enrollment
  • Tumor accessible for safe image-guided biopsies for whole genome and transcriptome sequencing
  • Negative serum pregnancy test within 14 days prior to randomization for pre-menopausal patients and agreement to use medically approved contraception during the study and 12 weeks after last SG dose
  • Measurable or non-measurable but assessable disease by CT or MRI as per RECIST 1.1 criteria
  • ECOG performance status of 0 to 2
  • Life expectancy of at least 3 months
  • Acceptable bone marrow and organ function: absolute neutrophil count ≥1.0 x 10^9/L, platelets ≥100 x 10^9/L, hemoglobin ≥9.0 g/dL, INR ≤1.5, serum creatinine clearance >50 mL/min, bilirubin ≤1.5 x ULN if no liver metastases, ALT and AST ≤2.5 x ULN (or <5.0 x ULN if liver metastases)
  • Controlled brain metastases allowed if stable for at least 4 weeks and no symptoms or high corticosteroid use
Not Eligible

You will not qualify if you...

  • Currently participating in other medical research incompatible with this study
  • Known hypersensitivity to sacituzumab govitecan, irinotecan, or SN-38
  • Unavailable for follow-up
  • Unwilling to consider systemic treatment options
  • Tumor not accessible or unsafe for biopsy
  • Unresolved acute toxic effects of prior anticancer therapy above CTCAE grade 1 (except stable grade 2 peripheral neuropathy)
  • Active second malignancy except certain treated or low-risk tumors
  • Active central nervous system metastases (except stable treated brain metastases)
  • Pregnancy or breastfeeding
  • Inadequate hematologic, renal, or hepatic function as per study criteria
  • Pre-existing uncontrolled diarrhea, chronic inflammatory bowel disease, or recent gastrointestinal perforation within 6 months
  • Active serious infection requiring antibiotic treatment

AI-Screening

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Trial Site Locations

Total: 1 location

1

BC Cancer - Vancouver Center

Vancouver, British Columbia, Canada, V5Z4E6

Actively Recruiting

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Research Team

S

Stephen Chia, MD

CONTACT

How is the study designed?

Study Type

INTERVENTIONAL

Masking

NONE

Allocation

NA

Model

SINGLE_GROUP

Primary Purpose

TREATMENT

Number of Arms

1

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