FDA approves tucatinib with trastuzumab and pertuzumab for 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. The FDA said the approval rests on HER2CLIMB-05, a randomized, double-blind, placebo-controlled trial in 654 adult patients.

What the FDA approved

The approved use is maintenance treatment. It applies to adults whose breast cancer is HER2-positive and either unresectable locally advanced or metastatic. Patients must have completed induction treatment first.

The FDA said the recommended tucatinib dosage is 300 mg orally twice daily in combination with trastuzumab and pertuzumab until disease progression or unacceptable toxicity. For dosing and administration of the combination agents, the FDA directs readers to the prescribing information of those agents.

The FDA said full prescribing information for Tukysa will be posted on Drugs@FDA. The FDA also said the review used the Assessment Aid, a voluntary submission from the applicant to support the FDA's assessment.

The trial design

The FDA said eligible patients had HER2-positive, unresectable locally advanced or metastatic breast cancer, with or without brain metastases. They also had 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. They received trastuzumab and pertuzumab intravenously, or a fixed-dose combination of trastuzumab, pertuzumab, and hyaluronidase given subcutaneously. The FDA said patients with hormone receptor positive disease were permitted to continue endocrine therapy. Patients were treated until disease progression or unacceptable toxicity.

The registry record for NCT05132582 lists the sponsor as Seagen, a wholly owned subsidiary of Pfizer. It describes a Phase 3 study with 654 participants, quadruple masking, and a start date of 2022-03-07. The record lists primary completion as 2025-09-05 and the status as active, not recruiting.

In the record, the experimental arm receives tucatinib 300 mg given orally twice daily plus trastuzumab and pertuzumab every 21 days. The control arm receives placebo given orally twice daily plus trastuzumab and pertuzumab every 21 days. The record lists ECOG performance status of 0 or 1 as an eligibility criterion.

Results as the FDA and the registry report them

The FDA said 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.

The FDA said 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. The FDA gave the hazard ratio as 0.64 (95% CI: 0.51, 0.80; p-value <0.0001). At the time of the PFS analysis, the FDA said OS data were not mature.

The registry record shows the same primary outcome. It posts 326 participants in the tucatinib arm and 328 in the placebo arm. It gives a hazard ratio of 0.641 (95% CI: 0.514-0.799) with p<0.0001.

The record also posts secondary outcomes. For PFS by blinded independent central review, the record lists a median of 28.9 months (95% CI: 24.3-NA) in the tucatinib arm and 16.0 months (95% CI: 12.3-22.9) in the placebo arm. The hazard ratio is 0.654, with p=0.0004.

For central nervous system PFS, the record says the median and 95% confidence interval could not be calculated because too few participants had events. It gives a hazard ratio of 0.846 and p=0.3041.

For treatment emergent adverse events, the record lists 323 of 326 participants in the tucatinib arm and 313 of 324 participants in the placebo arm.

Safety information in the label

The FDA said the prescribing information includes a boxed warning for hepatotoxicity. It also includes warnings and precautions for diarrhea, embryo-fetal toxicity, and increased serum creatinine without affecting renal function.

What comes next

The registry record lists overall survival and time to deterioration of health-related quality of life as secondary outcomes without posted results. The record gives an estimated final completion of 2027-09-28. The FDA page does not state a launch date or a price for the new use.