By Fineline Cube 
Pfizer Inc. (NYSE: PFE) today announced compelling topline results from the Phase 3 HER2CLIMB‑05 trial, evaluating the oral HER2 tyrosine‑kinase inhibitor TUKYSA (tucatinib) in combination with trastuzumab and pertuzumab as first‑line therapy for patients with HER2‑positive metastatic breast cancer (MBC).
Key Findings
| Metric | TUKYSA + Trastuzumab + Pertuzumab | Placebo + Trastuzumab + Pertuzumab |
|---|---|---|
| Primary Endpoint | Progression‑Free Survival (PFS) | PFS |
| Median PFS | 19.9 months | 14.7 months |
| Hazard Ratio | 0.70 (95% CI 0.58‑0.84) | – |
| Statistical Significance | p < 0.001 | – |
- Statistically significant improvement in investigator‑assessed PFS (HR 0.70, p < 0.001).
- Clinically meaningful 5‑month PFS advantage in the TUKYSA arm.
- Safety profile consistent with known TUKYSA, trastuzumab, and pertuzumab exposure; most common adverse events were diarrhea, nausea, and fatigue.
Trial Design
- Population: Adults with HER2‑positive MBC, treatment‑naïve for metastatic disease.
- Intervention: TUKYSA (oral 300 mg q.d.) plus trastuzumab + pertuzumab versus placebo plus trastuzumab + pertuzumab.
- Randomization: 1:1, stratified by visceral disease status.
- Primary Endpoint: Investigator‑assessed PFS per RECIST v1.1.
- Secondary Endpoints: Overall survival, objective response rate, duration of response, safety, and patient‑reported outcomes.
Implications for Clinical Practice
- First‑line evidence supporting TUKYSA as part of a dual‑HER2 blockade regimen.
- Potential to improve outcomes for patients with limited first‑line options, including those with brain metastases.
- Safety profile reinforces TUKYSA’s established tolerability in combination settings.
Forward‑Looking Statements
This release contains forward‑looking statements that involve risks and uncertainties. Actual results may differ materially.-Fineline Info & Tech