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Study of Trastuzumab Deruxtecan (DS-8201a, T-DXd) versus Investigator's Choice Chemotherapy in HER2-Low, Hormone Receptor Positive Breast Cancer Patients whose Disease has Progressed on Endocrine Therapy in the Metastatic Setting

Phase 3
Active, not recruiting
Conditions
HER2-Low, Hormone Receptor Positive Breast Cancer which has Progressed on Endocrine Therapy in the Metastatic Setting.
Registration Number
2024-516653-44-00
Lead Sponsor
AstraZeneca AB
Brief Summary

To assess the efficacy of Trastuzumab deruxtecan (T-DXd) compared with investigator's choice chemotherapy in terms of PFS by BICR in the HR+, HER2-low (IHC 2+/ISH- and IHC 1+) populations.

Detailed Description

Not available

Recruitment & Eligibility

Status
Ongoing, recruitment ended
Sex
Not specified
Target Recruitment
250
Inclusion Criteria

Patients must be ≥18 years of age.

Pathologically documented breast cancer that: a. is advanced or metastatic b. Has a history of HER2-low or negative expression, defined as IHC 2+/ISH- or IHC 1+ (ISH- or untested) or IHC 0 (ISH- or untested) c. Has HER2-low expression or HER2 IHC >0 <1+ expression as determined by the central laboratory result from a metastatic setting d. was never previously HER2-positive e. has documented HR+ disease in the metastatic disease setting.

Has adequate tumor samples for assessment of HER2 status

Disease progression on at least 2 previous lines of endocrine therapy with or without a targeted therapy (Progression of disease within 24 months on adjuvant ET is considered a line of therapy) or disease progression on endocrine therapy + CDK4/6 inhibitor within 6 months of starting first line treatment for metastatic disease and considered appropriate for chemotherapy as the next treatment by the investigator.

No prior chemotherapy for advanced or metastatic breast cancer.

Has protocol-defined adequate organ and bone marrow function. The most recent results must be used to meet this inclusion criteria

Exclusion Criteria

Ineligible for all options in the investigator's choice chemotherapy arm. Patients with contraindications to capecitabine, paclitaxel, and nabpaclitaxel treatment, per local prescribing information, cannot be enrolled

Uncontrolled intercurrent illness or significant cardiovascular disease

Active or prior documented ILD/pneumonitis that required steroids or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.

Lung-specific intercurrent clinically significant illnesses

Patients with spinal cord compression or active clinically central nervous system metastasis.

Concurrent enrolment in another clinical study, unless it is: - an observational (non-interventional) clinical study - during the follow up period of a prior interventional study (prescreening for this study while a patient is on treatment in another clinical study is acceptable)

Have received a study treatment from a prior interventional study, administered in the last 30 days prior to first dose of this study treatment

Study & Design

Study Type
Not specified
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
PFS by BICR according to RECIST 1.1 in the HR+, HER2-low population

PFS by BICR according to RECIST 1.1 in the HR+, HER2-low population

Secondary Outcome Measures
NameTimeMethod
Overall Survival (OS) - in HR+ HER2-low population

Overall Survival (OS) - in HR+ HER2-low population

Progression Free Survival (PFS) - in intent to treat (ITT) population (HER2 IHC >0 <1+ and HER2-low)

Progression Free Survival (PFS) - in intent to treat (ITT) population (HER2 IHC >0 <1+ and HER2-low)

OS - in ITT population (HER2 IHC >0 <1+ and HER2-low)

OS - in ITT population (HER2 IHC >0 <1+ and HER2-low)

Objective Response Rate (ORR) and Duration of response (DoR) - in HR+, HER-2 low population

Objective Response Rate (ORR) and Duration of response (DoR) - in HR+, HER-2 low population

PFS by Investigator assessment - in the HR+, HER2-low population

PFS by Investigator assessment - in the HR+, HER2-low population

ORR and DoR - in the ITT population

ORR and DoR - in the ITT population

PFS2 by Investigator assessment, time to first subsequent therapy (TFST) and time to second subsequent treatment or death (TSST) - in HR+, HER2-low and the ITT population

PFS2 by Investigator assessment, time to first subsequent therapy (TFST) and time to second subsequent treatment or death (TSST) - in HR+, HER2-low and the ITT population

Safety and tolerability of T-DXd compared to chemotherapy

Safety and tolerability of T-DXd compared to chemotherapy

The pharmacokinetics (PK) of T-Dxd

The pharmacokinetics (PK) of T-Dxd

Health-related quality of life

Health-related quality of life

Immunogenicity of T-Dxd

Immunogenicity of T-Dxd

Trial Locations

Locations (81)

Vitaz

🇧🇪

Sint-Niklaas, Belgium

Universitair Ziekenhuis Gent

🇧🇪

Gent, Belgium

Antwerp University Hospital

🇧🇪

Edegem, Belgium

UZ Leuven

🇧🇪

Leuven, Belgium

Algemeen Ziekenhuis Delta

🇧🇪

Roeselare, Belgium

Grand Hopital De Charleroi

🇧🇪

Charleroi, Belgium

Centre hospitalier universitaire de Liege

🇧🇪

Liege, Belgium

Cliniques Universitaires Saint-Luc

🇧🇪

Sint-Lambrechts-Woluwe, Belgium

Centre Hospitalier Universitaire Dinant Godinne Sainte-Elisabeth-UCL-Namur

🇧🇪

Namur, Belgium

Uppsala University Hospital

🇸🇪

Uppsala, Sweden

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Vitaz
🇧🇪Sint-Niklaas, Belgium
Ines Deleu
Site contact
003237602985
ines.deleu@vitaz.be

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