FDA approves tucatinib with trastuzumab and pertuzumab for the maintenance treatment of HER2-positive breast cancer

On October 7, 2026, the Food and Drug Administration approved tucatinib (Tukysa, Seagen Inc., a subsidiary of Pfizer) in combination with trastuzumab and pertuzumab for the maintenance treatment of adults with unresectable locally advanced or metastatic HER2-positive breast cancer following induction treatment.

Full prescribing information for Tukysa will be posted on Drugs@FDA .

Efficacy and Safety

Efficacy was evaluated in 654 adult patients in HER2CLIMB-05 (NCT05132582), a randomized, double-blind, placebo-controlled trial. Eligible patients were required to have HER2-positive, unresectable locally advanced or metastatic breast cancer, with or without brain metastases, and no evidence of disease progression by investigator assessment after induction treatment with 4-8 cycles of trastuzumab, pertuzumab, and a taxane. Patients received tucatinib 300 mg or placebo orally twice daily with trastuzumab and pertuzumab intravenously, or with a fixed-dose combination of trastuzumab, pertuzumab, and hyaluronidase administered subcutaneously. Patients with hormone receptor positive disease were permitted to continue endocrine therapy. Patients were treated until disease progression or unacceptable toxicity.

The primary efficacy outcome measure was progression-free survival (PFS) by investigator assessment using RECIST v1.1. Overall survival (OS) was an additional efficacy outcome measure. Median PFS was 24.9 months (95% CI: 21.3, not reached) in the tucatinib arm and 16.3 months (95% CI: 12.6, 18.7) in the placebo arm (Hazard ratio 0.64 [95% CI: 0.51, 0.80]; p-value <0.0001). At the time of PFS analysis, OS data were not mature.

The prescribing information includes a boxed warning for hepatotoxicity, as well as warnings and precautions for diarrhea, embryo-fetal toxicity, and increased serum creatinine without affecting renal function.

Recommended Dosage

The recommended tucatinib dosage is 300 mg orally twice daily in combination with trastuzumab and pertuzumab until disease progression or unacceptable toxicity. Refer to the prescribing information of the combination agents for dosing and administration information.

This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.