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TUKYSA, trastuzumab, and pertuzumab reduced the risk of disease progression or death by 36% compared to trastuzumab and pertuzumab alone in Phase 3 HER2CLIMB-05 study
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The combination demonstrated a manageable safety profile as a first-line maintenance therapy
December 10, 2025 - NEW YORK--(BUSINESS WIRE)-- Pfizer Inc. (NYSE: PFE) today announced detailed results from the Phase 3 HER2CLIMB-05 trial of the tyrosine kinase inhibitor TUKYSA® (tucatinib) as part of an investigational first-line maintenance treatment combination, following chemotherapy-based induction, in patients with human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC). The primary endpoint analysis showed 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, as assessed by the investigator (hazard ratio [HR] of 0.641, 95% confidence interval (CI): 0.514-0.799; 2-sided p<0.0001). These findings were published today in the Journal of Clinical Oncology, shared in an oral presentation at the 48th San Antonio Breast Cancer Symposium (SABCS), and highlighted in the SABCS official press program.
In HER2CLIMB-05, the median progression-free survival (PFS) was 24.9 months (95% CI: 21.3-not reached) in the TUKYSA arm and 16.3 months (95% CI:12.6-18.7) in the placebo arm, representing an extension in median PFS of 8.6 months. 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. 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.
“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.”
TUKYSA in combination with trastuzumab and pertuzumab demonstrated a safety profile generally consistent with the established safety profiles of each individual therapy, except for a higher rate of asymptomatic Grade ≥3 liver transaminases, which were typically manageable and reversible with TUKYSA dose modifications and/or discontinuations. The most common adverse events observed in the TUKYSA combination arm were diarrhea, hepatic events, and nausea.
“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.”
TUKYSA is not currently approved for first-line treatment. The results from HER2CLIMB-05 will be discussed 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; in the United States, TUKYSA is approved 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.
About HER2-Positive Metastatic Breast Cancer (MBC)
HER2 is overexpressed in up to 15-20% of breast cancers and is associated with poor prognosis, with an estimated five-year survival rate for HER2+ MBC of 41-47%, depending on HR status.1-3 First-line standard-of-care maintenance treatment has remained unchanged since 2012, and the majority of patients with HER2+ MBC face disease progression within two years of initiating therapy.4 Until recently, there have been limited advancements for these patients.
About the HER2CLIMB-05 Trial
HER2CLIMB-05 is a randomized, double blind, placebo-controlled, pivotal Phase 3 study evaluating the efficacy and safety of TUKYSA® (tucatinib) compared to placebo, both in combination with trastuzumab and pertuzumab, as maintenance therapy for patients with HER2+ MBC following induction therapy in the first-line setting.
Trial participants who completed induction therapy of trastuzumab, pertuzumab, and a taxane, with no evidence of progression were randomized to receive TUKYSA in combination with trastuzumab plus pertuzumab (n=326), or placebo in combination with trastuzumab plus pertuzumab (n=328). The primary endpoint is progression-free survival (PFS) as assessed by the investigator. Key secondary endpoints include overall survival.
About TUKYSA® (tucatinib)
TUKYSA (tucatinib) is an orally administered tyrosine kinase inhibitor of HER2. TUKYSA is approved in combination with trastuzumab and capecitabine to treat adults with HER2-positive advanced unresectable or metastatic breast cancer, including patients with brain metastases who have received one or more prior anti-HER2 breast cancer treatments in the metastatic setting.
About Pfizer Oncology
At Pfizer Oncology, we are at the forefront of a new era in cancer care. Our industry-leading portfolio and extensive pipeline includes three core mechanisms of action to attack cancer from multiple angles, including small molecules, antibody-drug conjugates (ADCs), and multispecific antibodies, including other immune-oncology biologics. We are focused on delivering transformative therapies in some of the world’s most common cancers, including breast cancer, genitourinary cancer, hematology-oncology, and thoracic cancers, which includes lung cancer. Driven by science, we are committed to accelerating breakthroughs to help people with cancer live better and longer lives.
About Pfizer: Breakthroughs That Change Patients’ Lives
At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development and manufacture of health care products, including innovative medicines and vaccines. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world’s premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For 175 years, we have worked to make a difference for all who rely on us.
References:
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Tarantino P, et al. ESMO expert consensus statements (ECS) on the definition, diagnosis, and management of HER2-low breast cancer. J An Onc. 2023;34(8):645-659.
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Wolff AC, et al. Human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline focused update. J Clin Oncol. 2018;36(20):2105-2122.
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National Cancer Institute. https://seer.cancer.gov/statfacts/html/breast-subtypes.html. Accessed October 8, 2025.
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Swain SM et al. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): End-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study. Lancet Oncol. 2020;21(4):519-530.