HER2-Low, Hormone Receptor Positive Breast Cancer which has Progressed on Endocrine Therapy in the Metastatic Setting. MedDRA version: 20.0 Level: SOC Classification code 10029104 Term: Neoplasms benign, malignant and unspecified (incl cysts and polyps) System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Key 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 by local test, defined as IHC 2+/ISH- or IHC 1+ (ISH- or untested) or HER2 IHC 0 (ISH- or untested) c. has HER2-low or HER2 IHC >0 =65 years) yes F.1.3.1 Number of subjects for this age range 85
Exclusion criteria
Exclusion criteria: Key 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: •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.;Secondary Objective: The key secondary objectives are: •OS in the HR+, HER2-low population •PFS by BICR and OS in the ITT population (HER2 IHC >0 <1+ and HER2-low) The other secondary objectives are: •PFS by Investigator assessment, ORR and DoR by BICR and Investigator assessment in the HR+, HER2-low population •ORR and DoR by BICR and Investigator assessment in the ITT population. •PFS2 according to Investigator assessment, time to first subsequent treatment or death (TFST) and time to second subsequent treatment or death (TSST) in the HR+, HER2-low population and the ITT population •the safety and tolerability profile of T-DXd compared with investigator’s choice chemotherapy •the PK of T-DXd •symptoms, functioning and HRQoL in patients treated with T-DXd compared with investigator’s choice single agent chemotherapy •the immunogenicity of T-DXd;Primary end point(s): •PFS by BICR according to RECIST 1.1 in the HR+, HER2-low population;Timepoint(s) of evaluation of this end point: Until progression or death, assessed up to approximately 60 months. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The key secondary endpoints are: 1. Overall Survival (OS) - in HR+ HER2-low population 2. Progression Free Survival (PFS) - in intent to treat (ITT) population (HER2 IHC >0 0 <1+ and HER2-low) The other secondary endpoints are: 1. Objective Response Rate (ORR) and Duration of response (DoR) - in HR+, HER-2 low population 2. PFS by Investigator assessment - in the HR+, HER2-low population 3. ORR and DoR - in the ITT population 4. 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 5. Safety and tolerability of T-DXd compared to chemotherapy. 6. The pharmacokinetics (PK) of T-Dxd 7. Health-related quality of life 8. Immunogenicity of T-Dxd;Timepoint(s) of evaluation of this end point: The timepoints for key secondary endpoints are: Please see section secondary endpoints for corresponding timepoints below 1. Until death, assessed up to approximately 60 months 2. Until progression or death, assessed up to approximately 60 months 3. Until death, assessed up to approximately 60 months The timepoints for other secondary endpoints are: 1. Until progression, assessed up to approximately 60 months 2. Until progression or death, assessed up to approximately 60 months 3. Until progression, assessed up to approximately 60 months 4. Assessed up to approximately 60 months 5. Up to follow-up period, approximately 60 months 6. Up to Cycle 8, approximately Week 24 7. Assessed up to approximately 60 months 8. Up to follow-up period, approximately 60 months | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, China, Denmark, France, Germany, Hungary, India, Israel, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Poland, Portugal, Russian Federation, Saudi Arabia, Spain, Sweden, Taiwan, United Kingdom, United States
Contacts
Public ContactStudy information Center
AstraZeneca
Outcome results
None listed