NEW YORK, NY — December 10, 2025 — Leads & Copy — Pfizer Inc. (NYSE: PFE) announced detailed results from the Phase 3 HER2CLIMB-05 trial of TUKYSA® (tucatinib), a tyrosine kinase inhibitor, as part of an investigational first-line maintenance treatment combination for patients with human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC).
The primary endpoint analysis revealed a 35.9% reduction in the risk of disease progression or death among patients treated with TUKYSA, trastuzumab, and pertuzumab, compared to those treated with placebo, trastuzumab, and pertuzumab. The investigator assessed a hazard ratio [HR] of 0.641, with a 95% confidence interval (CI) of 0.514-0.799; the 2-sided p-value was less than 0.0001.
According to Pfizer, these findings were published in the Journal of Clinical Oncology and shared in an oral presentation at the 48th San Antonio Breast Cancer Symposium (SABCS). The findings were also highlighted in the SABCS official press program.
In the HER2CLIMB-05 trial, the median progression-free survival (PFS) was 24.9 months (95% CI: 21.3-not reached) in the TUKYSA arm, while it was 16.3 months (95% CI: 12.6-18.7) in the placebo arm. This represents an extension in median PFS of 8.6 months. The company stated that a PFS benefit was observed across all prespecified patient subgroups, including de novo or recurrent diagnosis, hormone receptor (HR)-positive or HR-negative disease, and with or without the presence or history of brain metastases at baseline.
Pfizer noted that the key secondary endpoint of overall survival was not mature at the time of the analysis (20% of the required events have occurred to date) but showed a numerical trend for improvement with TUKYSA.
Erika Hamilton, M.D., principal investigator of HER2CLIMB-05 and Director of Breast Cancer Research for Sarah Cannon Research Institute (SCRI), said that the 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.
The company stated that the safety profile of TUKYSA, in combination with trastuzumab and pertuzumab, was generally consistent with the established safety profiles of each individual therapy, except for a higher rate of asymptomatic Grade ≥3 liver transaminases. These were typically manageable and reversible with TUKYSA dose modifications and/or discontinuations. Diarrhea, hepatic events, and nausea were cited as the most common adverse events observed in the TUKYSA combination arm.
Jeff Legos, Chief Oncology Officer at Pfizer, said that the results from HER2CLIMB-05 support TUKYSA’s potential use as part of a chemotherapy-free, front-line maintenance strategy.
TUKYSA is not currently approved for first-line treatment, but Pfizer plans to discuss the HER2CLIMB-05 results with regulatory authorities. Since its initial approval in 2020, TUKYSA, in combination with trastuzumab and capecitabine, has become a standard of care for HER2+ MBC patients in the third-line setting. TUKYSA is currently approved in more than 50 countries, including the United States, for use in combination with trastuzumab and capecitabine for adult patients with advanced unresectable or metastatic HER2+ breast cancer, including patients with brain metastases, who have received one or more prior anti-HER2-based regimens in the metastatic setting.
At Pfizer Oncology, the company says it is focused on delivering transformative therapies in some of the world’s most common cancers, including breast cancer, genitourinary cancer, hematology-oncology, and thoracic cancers, including lung cancer.
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Source: Pfizer Inc.
