Tuesday, October 14, 2025 - NEW YORK--(BUSINESS WIRE)-- Pfizer Inc. (NYSE: PFE) today announced positive topline results from the Phase 3 HER2CLIMB-05 trial of first-line combination therapy with the tyrosine kinase inhibitor TUKYSA® (tucatinib) in patients with human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC). HER2CLIMB-05 is evaluating TUKYSA versus placebo, both in combination with first-line standard-of-care maintenance therapy (trastuzumab plus pertuzumab) following chemotherapy-based induction. The trial met its primary endpoint, demonstrating a statistically significant and clinically meaningful improvement in progression-free survival (PFS) by investigator assessment in the TUKYSA arm versus the placebo arm. Treatment with TUKYSA in combination with trastuzumab and pertuzumab was tolerable, with a safety profile generally consistent with the established safety profiles of each individual therapy.
“HER2+ breast cancer is a particularly challenging subtype, with many patients experiencing disease progression despite effective treatments in the first-line setting,” said Erika Hamilton, M.D., principal investigator of HER2CLIMB-05 and Director, Breast Cancer Research, Sarah Cannon Research Institute (SCRI). “The HER2CLIMB-05 results demonstrate that the addition of TUKYSA to first-line maintenance therapy may further lower the risk of disease progression or death, with a treatment that has a well-established safety profile.”
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.i,ii,iii First-line standard of care maintenance treatment has remained unchanged since 2012, and the majority of HER2+ MBC patients face disease progression within two years of initiating therapy.iv Until recently, there have been limited advancements for these patients.
“Pfizer aims to help shape the future of front-line treatment for HER2+ MBC, where we see significant opportunity for a chemotherapy-free maintenance approach,” said Johanna Bendell, M.D., Chief Development Officer, Oncology, Pfizer. “The positive results from HER2CLIMB-05, combined with TUKYSA’s known safety profile in later-line settings, underscore its potential to play a meaningful role in front-line maintenance, where it may benefit a broader population of patients with HER2+ disease. We are grateful to the patients and investigators who contributed to this important research.”
Results from HER2CLIMB-05 will be presented at a future medical congress and discussed with regulatory authorities.
Since its initial approval in 2020, TUKYSA has become a standard of care for HER2+ MBC patients in the third-line setting and has been approved in more than 50 countries. In the United States, TUKYSA is approved by the U.S. Food and Drug Administration 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. TUKYSA is not currently approved for first-line treatment.
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+ metastatic breast cancer (MBC) following induction therapy in the first-line setting.
Study 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. Overall survival is a key secondary endpoint.
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.
iTarantino 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.
iiWolff 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.
iii National Cancer Institute. https://seer.cancer.gov/statfacts/html/breast-subtypes.html. Accessed October 8, 2025
ivSwain 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.