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OncoMatch/Clinical Trials/NCT06665178

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

Is NCT06665178 recruiting? Yes, currently enrolling (Jun 2026). This Phase 2 trial studies Sacituzumab Govitecan for breast cancer.

Phase 2RecruitingBritish Columbia Cancer AgencyNCT06665178Data as of Jun 2026Location: Canada

Treatment: Sacituzumab GovitecanAdvanced 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.

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Extracted eligibility criteria

Treatments studied

Targeted therapy

Sacituzumab Govitecan

Cancer type

Breast Carcinoma

Biomarker criteria

Required: ESR1 overexpression (ER+)

ER+/HER2 low (defined as IHC 1+ or 2+ but FISH or CISH negative by ratio as per ASCO/CAP guidelines)

Required: HER2 (ERBB2) low expression (IHC 1+ or 2+, FISH or CISH negative) (IHC 1+ or 2+, FISH or CISH negative)

HER2 low (defined as IHC 1+ or 2+ but FISH or CISH negative by ratio as per ASCO/CAP guidelines)

Disease stage

Metastatic disease required

Patients with locally advanced or metastatic ER+/HER2 low...breast cancer. Patients with imaging confirmed inoperable locally advanced breast cancer for which treatment is palliative in intent are also permitted.

Performance status

ECOG 0–2(Ambulatory, capable of self-care)

Prior therapy

Min 2 prior lines

Must have received: endocrine therapy — metastatic

Prior treatment must have included prior endocrine based treatment in the metastatic setting in conjunction with a CDK4/6 inhibitor.

Must have received: CDK4/6 inhibitor — metastatic

Prior treatment must have included prior endocrine based treatment in the metastatic setting in conjunction with a CDK4/6 inhibitor.

Must have received: chemotherapy

Prior treatment must include at least 1 line of chemotherapy which must include trastuzumab deruxtecan (T-DXd) as the immediate prior line of therapy prior to study enrollment

Must have received: antibody-drug conjugate (trastuzumab deruxtecan)

Prior treatment must include at least 1 line of chemotherapy which must include trastuzumab deruxtecan (T-DXd) as the immediate prior line of therapy prior to study enrollment

Lab requirements

Blood counts

Absolute neutrophil count ≥1.0 x 10^9/L; Platelets ≥100 x 10^9/L; Hemoglobin ≥9.0 g/dL; INR ≤1.5

Kidney function

Serum creatinine clearance >50 mL/min

Liver function

In absence of liver metastases, direct bilirubin ≤1.5 x ULN, ALT and AST should be below ≤2.5 x ULN. If the patient has liver metastases, ALT and AST should be < 5.0 x ULN.

Acceptable bone marrow and organ function defined by the following laboratory values: 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; In absence of liver metastases, direct bilirubin ≤1.5 x ULN, ALT and AST should be below ≤2.5 x ULN. If the patient has liver metastases, ALT and AST should be < 5.0 x ULN.

Structured fields extracted by AI. May contain errors — verify against the official protocol.

Frequently asked questions

Is NCT06665178 currently recruiting?

Yes, this trial is currently recruiting patients.

Is prior treatment required for enrollment?

Yes. Patients must have previously received endocrine therapy and CDK4/6 inhibitor.

Does this trial require ESR1?

Yes, ESR1 overexpression is a required biomarker for enrollment.

Does this trial require ERBB2?

Yes, ERBB2 low expression (IHC 1+ or 2+, FISH or CISH negative) is a required biomarker for enrollment.

Could you qualify for this trial?

Enter your biomarker results to see how this trial's eligibility criteria match your specific cancer profile.

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