Daiichi Sankyo
This study will evaluate a structured sequential treatment strategy starting with T-DXd + pertuzumab upfront therapy, followed by an optimized maintenance therapy with dual HER2+blockade + CDK4/6i + ET and the opportunity to retreat with T-DXd once patients progress under maintenance aimed to maximizing disease control, optimizing tolerability, and preserving T-DXd as a future therapeutic option, while ensuring participant safety and regulatory compliance in participants with HER2+/HR+ advanced/metastatic breast cancer.
This global, interventional, open-label, phase 3b trial will evaluate the efficacy and safety of a sequential treatment approach for first-line HER2+/HR+ advanced/metastatic breast cancer, initiating with upfront T-DXd + pertuzumab administered for 18 to 24 cycles, followed by a transition to trastuzumab + pertuzumab + ET + palbociclib. Participants who experience disease progression while receiving trastuzumab + pertuzumab + ET + palbociclib will receive T-DXd as 2L therapy. The study objectives will assess efficacy, safety, and quality-of-life in patients with advanced/metastatic breast can…
Key Inclusion Criteria for Upfront Treatment Phase 1. Sign and date the Main Trial informed consent form (ICF), prior to the start of any trial-specific procedures. 2. Participant must be ≥18 years of age at the time the ICF is signed. 3. Have pathologically documented breast cancer that: * Is locally advanced and unresectable or metastatic (participants who can be treated with curative intent are not eligible). * Participant must have histologically confirmed HER2+ and HR+ (ER+ and/or PR+), mBC. ER, PR, and HER2 measurements should be locally performed according to institutional guide…
Upfront treatment: One IV infusion Q3W 5.4 mg/kg (starting dose) on Day 1 of each 21-day cycle T-DXd Retreatment: One IV infusion Q3W 5.4 mg/kg (starting dose) on Day 1 of each 21-day cycle \*Dose reductions implemented during Upfront treatment phase will be maintained.
Maintenance treatment: One IV infusion Q3W 6 mg/kg on Day 1 of each 21-day cycle
Upfront treatment: One IV infusion Q3W loading dose of 840 mg, then 420 mg Q3W thereafter on Day 1 of each 21-day cycle Maintenance treatment: One IV infusion Q3W 420 mg on Day 1 of each 21-day cycle
Aromatase inhibitors or fulvestrant administered as approved product label
Maintenance treatment: Daily (3 out of 4 weeks, Q4W) oral 125 mg