Pfizer’s TUKYSA Delivers Significant PFS Benefit In Phase 3 HER2CLIMB-05 Trial; Tucatinib Combo Shows Extended First-Line Outcomes For HER2+ MBC

Pfizer has reported full Phase 3 findings from the HER2CLIMB-05 trial evaluating TUKYSA® (tucatinib) as part of an investigational first-line maintenance regimen for patients with HER2-positive metastatic breast cancer. The trial met its primary endpoint, showing that adding TUKYSA to trastuzumab and pertuzumab reduced the risk of disease progression or death by 35.9% compared with placebo plus the same antibodies. Investigators reported a hazard ratio of 0.641 with strong statistical significance.

“Most patients with HER2-positive metastatic breast cancer face disease progression within two years of starting first-line treatment, often requiring a transition to chemotherapy,” said Erika Hamilton, M.D., principal investigator of HER2CLIMB-05 and Director of Breast Cancer Research for Sarah Cannon Research Institute (SCRI). “These results demonstrate that adding tucatinib to first-line maintenance therapy extends the time patients live without their disease progressing, while maintaining a manageable safety profile, suggesting a promising new potential approach that could advance the current standard of care for HER2-positive disease.”

Patients receiving the TUKYSA-based regimen achieved a median progression-free survival of 24.9 months, compared with 16.3 months for those in the placebo arm, an 8.6-month improvement. The benefit was consistent across all predefined subgroups, including hormone receptor status, de novo versus recurrent disease, and patients with or without baseline brain metastases. Overall survival data remain immature, though early trends favor the TUKYSA arm.

Safety findings for the combination aligned largely with the known profiles of the included therapies. The most frequent adverse events were diarrhea, hepatic effects, and nausea. A higher incidence of asymptomatic Grade 3 or higher liver enzyme elevations was observed with TUKYSA; however, these events were typically reversible with dose adjustments or treatment discontinuation.

“TUKYSA has become a trusted standard of care for patients with later-line HER2-positive metastatic breast cancer, and the results from HER2CLIMB-05 support its potential use as part of a chemotherapy-free, front-line maintenance strategy,” said Jeff Legos, Chief Oncology Officer, Pfizer. “At Pfizer, we are committed to advancing treatment options that meaningfully improve the lives of people with metastatic breast cancer, and we are proud to share these promising results for patients and their families.”

Although TUKYSA is not yet approved for first-line use, these results will be submitted to regulatory authorities for review and consideration. The therapy is already well established in later-line treatment settings; since 2020, TUKYSA with trastuzumab and capecitabine has become a standard option for patients with HER2+ metastatic breast cancer, including those with brain metastases. The medicine is approved in more than 50 countries for these indications.