FDA News

FDA grants orphan drug designation to tucatinib for brain metastases

The FDA granted orphan drug designation to tucatinib for the treatment of patients with breast cancer whose disease metastasized to the brain, according to the drug’s manufacturer.

Tucatinib (ONT-380, Cascadian Therapeutics) is an investigational, orally bioavailable, potent tyrosine kinase inhibitor that is highly selective for HER-2 without significant inhibition of EGFR, which has been associated with significant toxicities.

“Brain metastases arise in up to 50% of women with HER-2–positive metastatic breast cancer, and these metastases can compromise quality of life and survival,” Eric P. Winer, MD, chief strategy officer and director of the Breast Oncology Center at Dana-Farber Cancer Institute, said in a Cascadian Therapeutics–issued press release.

Treatments for patients with brain metastases have been limited.

Tucatinib has demonstrated clinical activity as monotherapy, as well as in combination with chemotherapy and other HER-2–directed agents.

“There remains an unmet medical need for patients with HER-2–positive metastatic breast cancer, including patients whose disease has metastasized to the brain,” Scott Myers, president and CEO of Cascadian Therapeutics, said in the release. “New treatment options are clearly needed and tucatinib is being developed to fit within the current and emerging treatment paradigm.”

The ongoing randomized, double blind, placebo-controlled HER2CLIMB clinical trial is designed to compare capecitabine and trastuzumab (Herceptin, Genentech) with either tucatinib or placebo for patients with locally advanced or metastatic HER-2–positive breast cancer who underwent prior treatment with a taxane, trastuzumab, pertuzumab (Perjeta, Genentech) and ado-trastuzumab emtansine (Kadcyla, Genentech). PFS is the study’s primary endpoint.

“HER2CLIMB is enrolling patients with all types of brain metastases, including untreated, previously treated stable or progressing brain metastases,” Myers said. “Approximately half of patients enrolled in HER2CLIMB to date have had brain metastases at study entry, which will allow us to assess activity in that subpopulation in a statistically meaningful way. We are encouraged by results from our ongoing Phase 1b combination study of tucatinib plus capecitabine and/or trastuzumab, which showed a 42% response rate in patients with HER2-positive brain metastases.”

The FDA Office of Orphan Products Development grants orphan drug designation to novel drugs and biologics that are intended for the safe and effective treatment, diagnosis or prevention of rare diseases or disorders that affect fewer than 200,000 people in the United States. The designation allows manufacturers to qualify for various incentives, including tax credits for qualified clinical trials and — upon regulatory approval — 7 years of market exclusivity.

The FDA granted orphan drug designation to tucatinib for the treatment of patients with breast cancer whose disease metastasized to the brain, according to the drug’s manufacturer.

Tucatinib (ONT-380, Cascadian Therapeutics) is an investigational, orally bioavailable, potent tyrosine kinase inhibitor that is highly selective for HER-2 without significant inhibition of EGFR, which has been associated with significant toxicities.

“Brain metastases arise in up to 50% of women with HER-2–positive metastatic breast cancer, and these metastases can compromise quality of life and survival,” Eric P. Winer, MD, chief strategy officer and director of the Breast Oncology Center at Dana-Farber Cancer Institute, said in a Cascadian Therapeutics–issued press release.

Treatments for patients with brain metastases have been limited.

Tucatinib has demonstrated clinical activity as monotherapy, as well as in combination with chemotherapy and other HER-2–directed agents.

“There remains an unmet medical need for patients with HER-2–positive metastatic breast cancer, including patients whose disease has metastasized to the brain,” Scott Myers, president and CEO of Cascadian Therapeutics, said in the release. “New treatment options are clearly needed and tucatinib is being developed to fit within the current and emerging treatment paradigm.”

The ongoing randomized, double blind, placebo-controlled HER2CLIMB clinical trial is designed to compare capecitabine and trastuzumab (Herceptin, Genentech) with either tucatinib or placebo for patients with locally advanced or metastatic HER-2–positive breast cancer who underwent prior treatment with a taxane, trastuzumab, pertuzumab (Perjeta, Genentech) and ado-trastuzumab emtansine (Kadcyla, Genentech). PFS is the study’s primary endpoint.

“HER2CLIMB is enrolling patients with all types of brain metastases, including untreated, previously treated stable or progressing brain metastases,” Myers said. “Approximately half of patients enrolled in HER2CLIMB to date have had brain metastases at study entry, which will allow us to assess activity in that subpopulation in a statistically meaningful way. We are encouraged by results from our ongoing Phase 1b combination study of tucatinib plus capecitabine and/or trastuzumab, which showed a 42% response rate in patients with HER2-positive brain metastases.”

The FDA Office of Orphan Products Development grants orphan drug designation to novel drugs and biologics that are intended for the safe and effective treatment, diagnosis or prevention of rare diseases or disorders that affect fewer than 200,000 people in the United States. The designation allows manufacturers to qualify for various incentives, including tax credits for qualified clinical trials and — upon regulatory approval — 7 years of market exclusivity.