The U.S. Food and Drug Administration (FDA) approved Seattle Genetics’ Tukysa (tucatinib) in combination with chemotherapy agents trastuzumab and capecitabine for adults with HER2+ breast cancer that cannot be surgically removed or has metastasized to other parts of the body. The drug came out of Project Orbis, a multinational partnership between the FDA, the Australian Therapeutic Goods Administration (TGA), Health Canada, Health Sciences Authority (HSA, Singapore) and Swissmedic (SMC, Switzerland).
“We’re pleased to have collaborated with the FDA on our second expedited real-time oncology review, enabling us to rapidly bring this new targeted medicine to patients,” said Clay Siegall, chief executive officer of Seattle Genetics. “Tukysa has shown impressive results in people with HER2+ metastatic breast cancer, including in patients with active brain metastases, and offers patients an effective medicine following previous treatment with other anti-HER2 agents in the metastatic setting.”
The FDA is the first of the various agencies involved to approve the drug and it is the first Project Orbis partnership between the FDA, HSA and Swissmedic.
“The FDA’s Project Orbis provides a framework for concurrent submission and review of oncology drug applications among the FDA’s international collaborators,” stated Richard Pazdur, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research.
He went on to say, “We are pleased to work with our Singapore and Switzerland colleagues for the first time, and to continue working alongside our Australian and Canadian colleagues as we facilitate new treatment options for patients—like today’s first new molecular entity under Project Orbis.”
Tukysa is a kinase inhibitor and is approved for patients who have received one or more anti-HER2-based treatment in the metastatic setting. The approval was based on the HER2CLIMB clinical trial of 612 patients with HER2+ advanced unresectable or metastatic breast cancer who had previously been treated with trastuzumab, pertuzumab and ado-trastuzumab emtansine (T-DM1). Patients who had been treated and had stable brain metastases as well as patients with previously treated and growing or untreated brain metastases, were eligible for the trial. At the beginning of the trial, 48% of patients enrolled in the study had brain metastases.
The primary endpoint was progression-free survival (PFS). The median PFS in patients receiving Tukysa, trastuzumab and capecitabine was 7.8 months compared to 5.6 months in the patients who received placebo, trastuzumab and capecitabine. Median overall survival in the treatment group was 21.0 months compared to 17.4 months in the control cohort.
In addition to the international collaboration between the group, the review utilized the Real-Time Oncology Review (RTOR) pilot program. This program streamlines the submission of data before the completion and submission of the full clinical application. The RTOR and the Assessment Aid helped facilitate discussions between the various regulatory agencies and review process.
The FDA granted the application Priority Review and Breakthrough Therapy designation, as well as Fast Track designation and Orphan Drug designation.
HER2+ breast cancers have tumors with high levels of human epidermal growth factor receptor 2 (HER2). This promotes the growth of cancer cells. About 279,100 new cases of breast cancer are expected to be diagnosed in the U.S. this year, and between 15% and 20% are HER2+. These breast cancers are typically more aggressive and more likely to recur than HER2-negative breast cancer. Up to 50% of metastatic HER2+ breast cancer patients develop brain metastases.