Pfizer has announced positive topline results from its Phase 3 HER2CLIMB-05 trial evaluating TUKYSA (tucatinib) in combination with trastuzumab and pertuzumab as a first-line maintenance therapy for patients with HER2-positive (HER2+) metastatic breast cancer (MBC).

The study compared TUKYSA versus placebo, both in combination with first-line standard-of-care maintenance therapy (trastuzumab plus pertuzumab), following chemotherapy-based induction. According to Pfizer, the trial met its primary endpoint, showing a statistically significant and clinically meaningful improvement in progression-free survival (PFS) by investigator assessment in patients treated with the TUKYSA combination.

Treatment with TUKYSA in combination with trastuzumab and pertuzumab was well tolerated, and its safety was 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, 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,” she added.

Johanna Bendell, Chief Development Officer, Oncology, Pfizer, highlighted the company’s vision to advance front-line treatment approaches for HER2+ MBC, with a chemotherapy-free maintenance approach.

She said, “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.”

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 over 50 countries. In the United States, it 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.

TUKYSA is not yet approved for first-line use, but the HER2CLIMB-05 findings position it as a promising candidate for front-line maintenance therapy in HER2+ metastatic breast cancer.