A Study of Tucatinib or Placebo With Trastuzumab and Pertuzumab for Metastatic HER2+ Breast Cancer

Summary

This study is being done to see if tucatinib works better than placebo when given with other drugs to treat participants with HER2-positive breast cancer. A placebo is a pill that looks the same as tucatinib but has no medicine in it. This study will also test what side effects happen when participants take this combination of drugs. A side effect is anything a drug does to the body besides treating your disease. Participants will have cancer that has spread in the body near where it started (locally advanced) and cannot be removed (unresectable) or has spread through the body (metastatic). In this study, all participants will get either tucatinib or placebo. Participants will be assigned randomly to a group. This is a blinded study, so patients and their doctors will not know which group a participant is in. All participants will also get trastuzumab and pertuzumab. These are 2 drugs used to treat this type of cancer.

Timeline

Start

2022-03-07

Primary completion

2025-09-05

Completion

2027-09-28

Outcome

Met primary endpoint

paper In this primary analysis, PFS was statistically significantly improved with addition of tucatinib versus placebo PMID 41369677 ↗

paper hazard ratio, 0.641 [95% CI, 0.514 to 0.799]; P < .0001 PMID 41369677 ↗

release “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” pfizer.com ↗

release “The primary endpoint analysis showed a 35.9% reduction in the risk of disease progression or death” pfizer.com ↗

Publications

• Dieras V, Curigliano G, Martin M, Lerebours F, Tsurutani J, Savard MF, Jerzak KJ, Hu X, Martins de Aquino Pimentel LC, O'Sullivan CC, Tokunaga E, Okines A, Huang CS, Jacot W, Sohn J, Cronemberger Silva E, Mueller V, Yang S, Granata G, Shen Q, Santarpia L, Hamilton E; HER2CLIMB-05 Investigators. HER2CLIMB-05: A Phase III Study of Tucatinib Versus Placebo in Combination With Trastuzumab and Pertuzumab as First-Line Maintenance Therapy for HER2+ Metastatic Breast Cancer. J Clin Oncol. 2026 Jun 10;44(17):1597-1607. doi: 10.1200/JCO-25-02600. Epub 2025 Dec 10.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Tucatinib	Small molecule	300 mg	Oral
Background	Pertuzumab	Monoclonal antibody	420 mg	Intravenous
Background	Pertuzumab	Monoclonal antibody	600 mg	Subcutaneous
Background	Pertuzumab	Monoclonal antibody	20000 iu	Subcutaneous
Background	Trastuzumab	Monoclonal antibody	6 mg/kg	Intravenous
Background	Trastuzumab	Monoclonal antibody	600 mg	Intravenous

Indications