FDA News

FDA grants priority review to tucatinib for HER2-positive breast cancer

The FDA granted priority review to tucatinib, in combination with trastuzumab and capecitabine, for the treatment of patients with locally advanced or metastatic HER2-positive breast cancer, according to a press release from the agent’s manufacturer.

This indication applies to patients regardless of whether they have brain metastases who received at least three prior HER2-directed agents alone or in combination in any treatment setting.

Tucatinib (Seattle Genetics) is an investigational oral tyrosine kinase inhibitor that is highly selective for HER2 without significant inhibition of EGFR.

The FDA based its decision, in part, on data from the HER2CLIMB study, presented at last year’s San Antonio Breast Cancer Symposium.

As Healio previously reported, researchers evaluated the addition of tucatinib to trastuzumab (Herceptin, Genentech) plus capecitabine among 612 patients with locally advanced or metastatic HER2-positive breast cancer who received prior treatment with trastuzumab, pertuzumab (Perjeta, Genentech) and ado-trastuzumab emtansine (Kadcyla, Genentech).

Results showed the addition of tucatinib to trastuzumab and capecitabine conferred a statistically significant improvement in PFS (median, 7.8 months vs. 5.6 months; HR = 0.54; 95% CI, 0.42-0.71), including among patients with brain metastases (median, 7.6 months vs. 5.4 months; HR = 0.48; 95% CI, 0.34-0.69).

Tucatinib appeared associated with a 34% reduction in risk for death (median OS, 21.9 months vs. 17.4 months; HR = 0.66; 95% CI, 0.5-0.88) and a significantly higher overall response rate (41% vs. 23%; P = .00008).

“The FDA’s filing of the tucatinib [new drug application] marks an important step forward for patients with locally advanced or metastatic HER2-positive breast cancer, including those with brain metastases,” Clay Siegall, PhD, president and CEO of Seattle Genetics, said in the release. “We are working collaboratively with the FDA throughout the review process to bring this important medicine to patients as quickly as possible.”

Tucatinib also is being evaluated in combination with ado-trastuzumab emtansine for patients with unresectable locally advanced or metastatic HER2-positive breast cancer in the phase 3 HER2CLIMB-02 trial, and in combination with trastuzumab for patients with HER2-positive, RAS-wild-type metastatic or unresectable colorectal cancer in the phase 2 MOUNTAINEER study.

Tucatinib previously received breakthrough therapy designation for this indication and orphan drug designation for the treatment of patients with brain metastases from breast cancer.

The FDA — which is reviewing tucatinib under the Real-Time Oncology Review Pilot Program and Project Orbis, an initiative that enables concurrent submission and review of oncology drugs among international partners — set an action date for this application of Aug. 20.

The FDA granted priority review to tucatinib, in combination with trastuzumab and capecitabine, for the treatment of patients with locally advanced or metastatic HER2-positive breast cancer, according to a press release from the agent’s manufacturer.

This indication applies to patients regardless of whether they have brain metastases who received at least three prior HER2-directed agents alone or in combination in any treatment setting.

Tucatinib (Seattle Genetics) is an investigational oral tyrosine kinase inhibitor that is highly selective for HER2 without significant inhibition of EGFR.

The FDA based its decision, in part, on data from the HER2CLIMB study, presented at last year’s San Antonio Breast Cancer Symposium.

As Healio previously reported, researchers evaluated the addition of tucatinib to trastuzumab (Herceptin, Genentech) plus capecitabine among 612 patients with locally advanced or metastatic HER2-positive breast cancer who received prior treatment with trastuzumab, pertuzumab (Perjeta, Genentech) and ado-trastuzumab emtansine (Kadcyla, Genentech).

Results showed the addition of tucatinib to trastuzumab and capecitabine conferred a statistically significant improvement in PFS (median, 7.8 months vs. 5.6 months; HR = 0.54; 95% CI, 0.42-0.71), including among patients with brain metastases (median, 7.6 months vs. 5.4 months; HR = 0.48; 95% CI, 0.34-0.69).

Tucatinib appeared associated with a 34% reduction in risk for death (median OS, 21.9 months vs. 17.4 months; HR = 0.66; 95% CI, 0.5-0.88) and a significantly higher overall response rate (41% vs. 23%; P = .00008).

“The FDA’s filing of the tucatinib [new drug application] marks an important step forward for patients with locally advanced or metastatic HER2-positive breast cancer, including those with brain metastases,” Clay Siegall, PhD, president and CEO of Seattle Genetics, said in the release. “We are working collaboratively with the FDA throughout the review process to bring this important medicine to patients as quickly as possible.”

Tucatinib also is being evaluated in combination with ado-trastuzumab emtansine for patients with unresectable locally advanced or metastatic HER2-positive breast cancer in the phase 3 HER2CLIMB-02 trial, and in combination with trastuzumab for patients with HER2-positive, RAS-wild-type metastatic or unresectable colorectal cancer in the phase 2 MOUNTAINEER study.

Tucatinib previously received breakthrough therapy designation for this indication and orphan drug designation for the treatment of patients with brain metastases from breast cancer.

The FDA — which is reviewing tucatinib under the Real-Time Oncology Review Pilot Program and Project Orbis, an initiative that enables concurrent submission and review of oncology drugs among international partners — set an action date for this application of Aug. 20.