Based on the Phase 2a trial results, how does zanidatamab, in combination with palbociclib and fulvestrant, redefine treatment approaches for heavily pretreated HER2-positive/HR-positive mBC patients?

The trial demonstrated a progression-free survival of 67% at 6 months and a median PFS of 12 months. How significant are these results in the context of current treatment options for this patient population?

Can you elaborate on the dual mechanism of action of zanidatamab and its significance in achieving these promising trial outcomes?

With a reported confirmed objective response rate of 35%, what insights can you provide about the response variability among patients? Are there identifiable factors that may predict a patient's response to this treatment regimen?

The trial indicated a manageable safety profile for the combination therapy. Could you discuss the key safety concerns observed and how they compare to other treatments for metastatic breast cancer?

How does the absence of chemotherapy in this combination therapy impact the quality of life and overall treatment experience for patients?

Given the breakthrough therapy designations for zanidatamab in other indications, what future directions do you foresee for this drug in the broader landscape of HER2-positive cancers?

In light of the trial results, what are the next steps in the clinical development of zanidatamab for HER2-positive/HR-positive mBC, and what potential barriers might impact its progress towards wider clinical application?