Seattle Genetics, Inc. recently issued the following announcement.
– Submission Based on Positive Pivotal HER2CLIMB Trial Results Recently Presented at the 2019 San Antonio Breast Cancer Symposium and Published in the New England Journal of Medicine –
– FDA Granted Breakthrough Therapy Designation for Tucatinib in Locally Advanced or Metastatic HER2-Positive Breast Cancer –
– First Investigational Therapy in a Pivotal Trial to Address Unmet Need for Patients with Metastatic HER2-Positive Breast Cancer with or without Brain Metastases –
Seattle Genetics, Inc. (Nasdaq:SGEN) today announced it has completed the submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for tucatinib. This NDA requests FDA approval of tucatinib in combination with trastuzumab and capecitabine for treatment of patients with locally advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have received at least three prior HER2-directed agents separately or in combination, in the neoadjuvant, adjuvant or metastatic setting. The submission is based on the results of HER2CLIMB, a randomized pivotal trial comparing tucatinib added to trastuzumab and capecitabine versus trastuzumab and capecitabine alone. HER2CLIMB trial results were presented on December 11, 2019 at the 2019 San Antonio Breast Cancer Symposium and published in the New England Journal of Medicine. Tucatinib is an oral, small molecule tyrosine kinase inhibitor (TKI) that is highly selective for HER2.
Tucatinib was recently granted Breakthrough Therapy designation by the FDA in combination with trastuzumab and capecitabine, for treatment of patients with locally advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have been treated with trastuzumab, pertuzumab, and T-DM1. This designation was based on data from the HER2CLIMB trial.
“Today’s submission marks another important milestone for Seattle Genetics and tucatinib, and a potential advance for patients with either locally advanced or metastatic HER2-positive breast cancer, including those with and without brain metastases,” said Roger Dansey, M.D., Chief Medical Officer at Seattle Genetics. “We look forward to working with the FDA on the review of this application.”
About HER2-Positive Breast Cancer
Patients with HER2-positive breast cancer have tumors with high levels of a protein called human epidermal growth factor receptor 2 (HER2), which promotes the aggressive spread of cancer cells. An estimated 271,270 new cases of invasive breast cancer will be diagnosed in the U.S. in 2019.1 Between 15 and 20 percent of breast cancer cases worldwide are HER2-positive.2 Historically, HER2-positive breast cancer tends to be more aggressive and more likely to recur than HER2-negative breast cancer.2, 3, 4 In patients with metastatic breast cancer, the most common site of first metastasis is in bone, followed by lung, brain, and liver.5, 6 Up to 50 percent of metastatic HER2-positive breast cancer patients develop brain metastases over time.2, 7 Despite recent treatment advances, there is still a significant need for new therapies that can impact metastatic disease, especially brain metastases. There are currently no approved therapies demonstrating progression-free survival or overall survival benefit for the treatment of patients with HER2-positive metastatic breast cancer after progression on T-DM1.8, 9, 10
About HER2CLIMB
HER2CLIMB is a multinational randomized (2:1), double-blind, placebo-controlled, active comparator, pivotal clinical trial comparing tucatinib in combination with trastuzumab and capecitabine compared with trastuzumab and capecitabine alone in patients with locally advanced unresectable or metastatic HER2-positive breast cancer who were previously treated with trastuzumab, pertuzumab, and T-DM1. The primary endpoint of the trial was PFS per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as determined by blinded independent central review (BICR) in the first 480 patients enrolled in the trial. HER2CLIMB enrolled a total of 612 patients to support the analyses of key secondary endpoints, including overall survival, PFS per BICR in patients with brain metastases at baseline, and confirmed objective response rate. Safety data were evaluated throughout the study.
About Tucatinib
Tucatinib is an investigational, orally bioavailable, potent tyrosine kinase inhibitor that is highly selective for HER2 without significant inhibition of EGFR. Inhibition of EGFR has been associated with significant toxicities, including skin rash and diarrhea. Tucatinib has shown activity as a single agent and in combination with both chemotherapy and other HER2 targeted agents such as trastuzumab.1, 2 Studies of tucatinib in these combinations have shown activity both systemically and in brain metastases. HER2 is a growth factor receptor that is overexpressed in multiple cancers, including breast, colorectal, and gastric cancers. HER2 mediates cell growth, differentiation, and survival. Tucatinib has been granted orphan drug designation by the FDA for the treatment of breast cancer patients with brain metastases.
In addition to HER2CLIMB, tucatinib is being evaluated in a randomized, double-blind, placebo-controlled, multi-center phase 3 trial of tucatinib in combination with T-DM1 compared to T-DM1 alone, in patients with unresectable locally advanced or metastatic HER2-positive breast cancer, including those with brain metastases, who have had prior treatment with a taxane and trastuzumab. The primary endpoint is progression-free survival per RECIST criteria. Secondary endpoints include overall survival, objective response rate, and duration of response. The trial is being conducted in North America and is expected to enroll approximately 460 patients. More information about the phase 3 trial, including enrolling centers, is available at www.clinicaltrials.gov.
Tucatinib is also being evaluated in a multi-center, open-label, single-arm phase 2 clinical trial known as MOUNTAINEER, which is evaluating tucatinib in combination with trastuzumab in patients with HER2-positive, RAS wildtype metastatic, or unresectable colorectal cancer. The primary endpoint of the trial is objective response rate by RECIST criteria. Progression-free survival, duration of response, overall survival, and safety and tolerability of the combination regimen are secondary objectives. Results for 26 patients were evaluated in an analysis and presented at the European Society for Medical Oncology (ESMO) 2019 Congress. Enrollment is ongoing. More information about the MOUNTAINEER trial, including enrolling centers, is available at www.clinicaltrials.gov.
About Seattle Genetics
Seattle Genetics, Inc. is a global biotechnology company that discovers, develops, and commercializes transformative medicines targeting cancer to make a meaningful difference in people’s lives. ADCETRIS® (brentuximab vedotin) and PADCEV™ (enfortumab vedotin-ejfv) use the company’s industry-leading antibody-drug conjugate (ADC) technology designed to bring a powerful medicine directly to cancer cells. ADCETRIS is approved for the treatment of several types of CD30-expressing lymphomas, and PADCEV is approved to treat adults with metastatic urothelial cancer. In addition, investigational agent tucatinib, a small molecule tyrosine kinase inhibitor, is in late-stage development for HER2-positive metastatic breast cancer, and in clinical development for metastatic colorectal cancer. The company is headquartered in Bothell, Washington, and has offices in California, Switzerland, and the European Union. For more information on our robust pipeline, visit www.seattlegenetics.com and follow @SeattleGenetics on Twitter.
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