TRASTUZUMAB DERUXTECAN for Breast cancer (hormone receptor-positive, HER2-low, metastatic)

Inclusion criteria

• {"criterion_text":"- Patients must be ≥18 years of age.\n- 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.\n- Has adequate tumor samples for assessment of HER2 status\n- 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.\n- No prior chemotherapy for advanced or metastatic breast cancer.\n- Has protocol-defined adequate organ and bone marrow function. The most recent results must be used to meet this inclusion criteria"}

Exclusion criteria

• {"criterion_text":"- 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\n- Uncontrolled intercurrent illness or significant cardiovascular disease\n- Active or prior documented ILD/pneumonitis that required steroids or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.\n- Lung-specific intercurrent clinically significant illnesses\n- Patients with spinal cord compression or active clinically central nervous system metastasis.\n- 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)\n- Have received a study treatment from a prior interventional study, administered in the last 30 days prior to first dose of this study treatment"}

Primary endpoints

• {"endpoint_text":"- PFS by BICR according to RECIST 1.1 in the HR+, HER2-low population","definition_or_measurement_approach":"Progression-free survival determined by Blinded Independent Central Review (BICR) using RECIST 1.1"}

Secondary endpoints

• {"endpoint_text":"- Overall Survival (OS) - in HR+ HER2-low population","definition_or_measurement_approach":"Overall survival (time from randomisation to death) in the HR+, HER2-low population"}
• {"endpoint_text":"- Progression Free Survival (PFS) - in intent to treat (ITT) population (HER2 IHC >0 <1+ and HER2-low)","definition_or_measurement_approach":"PFS assessed in ITT population (HER2 IHC >0 <1+ and HER2-low), measurement method not further specified (primary PFS used BICR/RECIST 1.1)"}
• {"endpoint_text":"- OS - in ITT population (HER2 IHC >0 <1+ and HER2-low)","definition_or_measurement_approach":"Overall survival in ITT population"}
• {"endpoint_text":"- Objective Response Rate (ORR) and Duration of response (DoR) - in HR+, HER-2 low population","definition_or_measurement_approach":"ORR and DoR assessed by BICR and investigator assessment in HR+, HER2-low population"}
• {"endpoint_text":"- PFS by Investigator assessment - in the HR+, HER2-low population","definition_or_measurement_approach":"PFS assessed by investigator (per RECIST 1.1) in HR+, HER2-low population"}
• {"endpoint_text":"- ORR and DoR - in the ITT population","definition_or_measurement_approach":"ORR and DoR assessed in ITT population (methods include BICR and investigator assessment)"}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"PFS2, TFST and TSST assessed by investigator in HR+, HER2-low and ITT populations"}
• {"endpoint_text":"- Safety and tolerability of T-DXd compared to chemotherapy","definition_or_measurement_approach":"Safety and tolerability assessed by adverse events, lab values, and clinical assessments (specific measurements not detailed in JSON)"}
• {"endpoint_text":"- The pharmacokinetics (PK) of T-Dxd","definition_or_measurement_approach":"Pharmacokinetic characterization of T-DXd (PK sampling and analysis as per protocol; details not provided in JSON)"}
• {"endpoint_text":"- Health-related quality of life","definition_or_measurement_approach":"HRQoL measured using patient reported outcome instruments (patient-facing questionnaires available in multiple languages listed in trial documents)"}
• {"endpoint_text":"- Immunogenicity of T-Dxd","definition_or_measurement_approach":"Assessment of immunogenicity (anti-drug antibodies etc.); specific assays/methods not provided in JSON"}

Primary sponsor

Full Name

AstraZeneca AB

Organisation Type

Pharmaceutical company

Country Of Registered Address

Sweden