-Approved for Patients with HER2-Positive Metastatic Breast Cancer Who Have Received One or More Prior Anti-HER2 Therapies in the Metastatic Setting-
-First HER-2 Tyrosine Kinase Inhibitor in Combination to Improve Overall and Progression-Free Survival in Patients with Metastatic HER2-Positive Breast Cancer With or Without Brain Metastases-
-Application Approved Four Months Prior to Action Date Under FDA’s Real-Time Oncology Review (RTOR)-
BOTHELL, WA, USA I April 17, 2020 I Seattle Genetics, Inc. (Nasdaq:SGEN) today announced the U.S. Food and Drug Administration (FDA) granted approval to TUKYSA™ (tucatinib) tablets in combination with trastuzumab and capecitabine for adult patients with advanced unresectable (cannot be surgically removed) or metastatic HER2-positive breast cancer, including patients with brain metastases (disease that has spread to the brain), who have received one or more prior anti-HER2-based regimens in the metastatic setting. The FDA previously granted Breakthrough Therapy designation and Priority Review for TUKYSA and reviewed this application for approval under the Real-Time Oncology Review (RTOR) pilot program. The TUKYSA New Drug Application (NDA) is also part of Project Orbis, an initiative of the FDA Oncology Center of Excellence that provides a framework for concurrent submission and review of oncology drugs among participating international health authorities. TUKYSA is an oral, small molecule tyrosine kinase inhibitor (TKI) of HER2, a protein that contributes to cancer cell growth.1,2
“With highly significant and clinically important results for overall and progression-free survival, the addition of TUKYSA to trastuzumab and capecitabine has the potential to become a standard of care for people with HER2-positive metastatic breast cancer after having received one or more previous anti-HER2 therapies in the metastatic setting,” said Eric P. Winer, MD, Chief of the Division of Breast Oncology, Susan F. Smith Center for Women’s Cancers at Dana-Farber. “Cancer spreads to the brain in up to half of patients with HER2-positive metastatic breast cancer; and this approval is based on a unique clinical trial that included patients with active brain metastases, either untreated or progressing. TUKYSA is well tolerated by patients and is a valuable addition to the agents we have for HER2-positive metastatic breast cancer.”
“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, Ph.D., Chief Executive Officer at Seattle Genetics. “TUKYSA has shown impressive results in people with HER2-positive 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.”
TUKYSA, in combination with trastuzumab and capecitabine, was evaluated in the trial HER2CLIMB, a randomized (2:1), double-blind, placebo-controlled trial that enrolled 612 patients with HER2-positive unresectable locally advanced or metastatic breast cancer who had previously received, either separately or in combination, trastuzumab, pertuzumab, and ado-trastuzumab emtansine (T-DM1). Forty-eight percent of patients in the study had a presence or history of brain metastases. The primary efficacy outcome measure was progression-free survival (PFS) as assessed by blinded independent central review (BICR) in the first 480 randomized patients.1 Additional efficacy outcome measures were evaluated in all randomized patients and included overall survival (OS), PFS in patients with a history or presence of brain metastases, and confirmed objective response rate (ORR).
Patients who received TUKYSA in combination with trastuzumab and capecitabine had a 46 percent reduction in the risk of cancer progression or death (PFS) compared to patients who received trastuzumab and capecitabine alone (hazard ratio (HR)=0.54 [95% Confidence Interval (CI): 0.42, 0.71]; p<0.00001). The addition of TUKYSA reduced the risk of death (OS) by 34 percent compared to trastuzumab and capecitabine alone (HR=0.66 [95% CI: 0.50, 0.87]; p=0.0048). Nearly twice the number of patients who received TUKYSA in combination with trastuzumab and capecitabine had a confirmed objective response compared to those who received trastuzumab and capecitabine alone (40.6 percent (95% CI: 35.3, 46.0) vs. 22.8 percent (95% CI: 16.7, 29.8); p=0.00008). For patients with brain metastases, the addition of TUKYSA reduced the risk of cancer progression or death (PFS) by 52 percent compared to trastuzumab and capecitabine alone (HR=0.48 [95% CI: 0.34, 0.69]; p<0.00001).
Serious adverse reactions occurred in 26 percent of patients who received TUKYSA. Serious adverse reactions occurring in 2 percent or more of patients who received TUKYSA were diarrhea (4%), vomiting (2.5%), nausea, abdominal pain, and seizure (2% each). The most common adverse reactions occurring in 20 percent or more of patients who received TUKYSA were diarrhea, palmar-plantar erythrodysesthesia, nausea, fatigue, hepatotoxicity, vomiting, stomatitis, decreased appetite, abdominal pain, headache, anemia, and rash. Adverse reactions leading to treatment discontinuation occurred in 6 percent of patients who received TUKYSA; adverse reactions leading to treatment discontinuation of TUKYSA (in 1 percent or more of patients) were hepatotoxicity (1.5%) and diarrhea (1%).
The data were published in The New England Journal of Medicinein December 2019.
About TUKYSA (tucatinib)
TUKYSA is an oral medicine that is a tyrosine kinase inhibitor of the HER2 protein. In vitro (in lab studies), TUKYSA inhibited phosphorylation of HER2 and HER3, resulting in inhibition of downstream MAPK and AKT signaling and cell growth (proliferation), and showed anti-tumor activity in HER2-expressing tumor cells. In vivo (in living organisms), TUKYSA inhibited the growth of HER2-expressing tumors. The combination of TUKYSA and the anti-HER2 antibody trastuzumab showed increased anti-tumor activity in vitro and in vivo compared to either medicine alone.1
SeaGen Secure offers access and reimbursement support to help patients access TUKYSA. For more information, go to SeaGenSecure.com.
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 growth of cancer cells. An estimated 279,100 new cases of breast cancer will be diagnosed in the U.S. in 2020.3 Between 15 and 20 percent of breast cancer cases are HER2-positive.3 Historically, HER2-positive breast cancer tends to be more aggressive and more likely to recur than HER2-negative breast cancer.4,5,6 Up to 50 percent of metastatic HER2-positive breast cancer patients develop brain metastases over time.7,8,9
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. 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.
[1] TUKYSA [package insert]. Bothell, WA: Seattle Genetics, Inc.
[2] Anita Kulukian, Patrice Lee, Janelle Taylor, et al. Preclinical Activity of HER2-Selective Tyrosine Kinase Inhibitor Tucatinib as a Single Agent or in Combination with Trastuzumab or Docetaxel in Solid Tumor ModelsMol Cancer Ther 2020;19:976-987.
[3] Cancer Facts & Figures 2020. American Cancer Society website. https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2020/cancer-facts-and-figures-2020.pdf. Accessed March 10, 2020.
[3] Loibli S, Gianni L. HER2-positive breast cancer. Lancet. 2017; 389(10087): 2415-29.
[4] Slamon D, Clark G, Wong S, et al. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987; 235(4785): 177-82.
[5] Breast Cancer HER2 Status. American Cancer Society website. https://www.cancer.org/cancer/breast-cancer/understanding-a-breast-cancer-diagnosis/breast-cancer-her2-status.html. Accessed March 9, 2020.
[6] Freedman RA, Gelman RS, Anders CK, et al. TBCRC 022: a phase II trial of neratinib and capecitabine for patients with human epidermal growth factor receptor 2-positive breast cancer and brain metastases. J Clin Oncol. 2019;37:1081-1089.
[7] Olson EM, Najita JS, Sohl J, et al. Clinical outcomes and treatment practice patterns of patients with HER2-positive metastatic breast cancer in the post-trastuzumab era. Breast. 2013;22:525-531.
[8] Bendell JC, Domchek SM, Burstein HJ, et al. Central nervous system metastases in women who receive trastuzumab-based therapy for metastatic breast carcinoma. Cancer. 2003;97:2972-2977.
SOURCE: Seattle Genetics
Post Views: 119
-Approved for Patients with HER2-Positive Metastatic Breast Cancer Who Have Received One or More Prior Anti-HER2 Therapies in the Metastatic Setting-
-First HER-2 Tyrosine Kinase Inhibitor in Combination to Improve Overall and Progression-Free Survival in Patients with Metastatic HER2-Positive Breast Cancer With or Without Brain Metastases-
-Application Approved Four Months Prior to Action Date Under FDA’s Real-Time Oncology Review (RTOR)-
BOTHELL, WA, USA I April 17, 2020 I Seattle Genetics, Inc. (Nasdaq:SGEN) today announced the U.S. Food and Drug Administration (FDA) granted approval to TUKYSA™ (tucatinib) tablets in combination with trastuzumab and capecitabine for adult patients with advanced unresectable (cannot be surgically removed) or metastatic HER2-positive breast cancer, including patients with brain metastases (disease that has spread to the brain), who have received one or more prior anti-HER2-based regimens in the metastatic setting. The FDA previously granted Breakthrough Therapy designation and Priority Review for TUKYSA and reviewed this application for approval under the Real-Time Oncology Review (RTOR) pilot program. The TUKYSA New Drug Application (NDA) is also part of Project Orbis, an initiative of the FDA Oncology Center of Excellence that provides a framework for concurrent submission and review of oncology drugs among participating international health authorities. TUKYSA is an oral, small molecule tyrosine kinase inhibitor (TKI) of HER2, a protein that contributes to cancer cell growth.1,2
“With highly significant and clinically important results for overall and progression-free survival, the addition of TUKYSA to trastuzumab and capecitabine has the potential to become a standard of care for people with HER2-positive metastatic breast cancer after having received one or more previous anti-HER2 therapies in the metastatic setting,” said Eric P. Winer, MD, Chief of the Division of Breast Oncology, Susan F. Smith Center for Women’s Cancers at Dana-Farber. “Cancer spreads to the brain in up to half of patients with HER2-positive metastatic breast cancer; and this approval is based on a unique clinical trial that included patients with active brain metastases, either untreated or progressing. TUKYSA is well tolerated by patients and is a valuable addition to the agents we have for HER2-positive metastatic breast cancer.”
“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, Ph.D., Chief Executive Officer at Seattle Genetics. “TUKYSA has shown impressive results in people with HER2-positive 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.”
TUKYSA, in combination with trastuzumab and capecitabine, was evaluated in the trial HER2CLIMB, a randomized (2:1), double-blind, placebo-controlled trial that enrolled 612 patients with HER2-positive unresectable locally advanced or metastatic breast cancer who had previously received, either separately or in combination, trastuzumab, pertuzumab, and ado-trastuzumab emtansine (T-DM1). Forty-eight percent of patients in the study had a presence or history of brain metastases. The primary efficacy outcome measure was progression-free survival (PFS) as assessed by blinded independent central review (BICR) in the first 480 randomized patients.1 Additional efficacy outcome measures were evaluated in all randomized patients and included overall survival (OS), PFS in patients with a history or presence of brain metastases, and confirmed objective response rate (ORR).
Patients who received TUKYSA in combination with trastuzumab and capecitabine had a 46 percent reduction in the risk of cancer progression or death (PFS) compared to patients who received trastuzumab and capecitabine alone (hazard ratio (HR)=0.54 [95% Confidence Interval (CI): 0.42, 0.71]; p<0.00001). The addition of TUKYSA reduced the risk of death (OS) by 34 percent compared to trastuzumab and capecitabine alone (HR=0.66 [95% CI: 0.50, 0.87]; p=0.0048). Nearly twice the number of patients who received TUKYSA in combination with trastuzumab and capecitabine had a confirmed objective response compared to those who received trastuzumab and capecitabine alone (40.6 percent (95% CI: 35.3, 46.0) vs. 22.8 percent (95% CI: 16.7, 29.8); p=0.00008). For patients with brain metastases, the addition of TUKYSA reduced the risk of cancer progression or death (PFS) by 52 percent compared to trastuzumab and capecitabine alone (HR=0.48 [95% CI: 0.34, 0.69]; p<0.00001).
Serious adverse reactions occurred in 26 percent of patients who received TUKYSA. Serious adverse reactions occurring in 2 percent or more of patients who received TUKYSA were diarrhea (4%), vomiting (2.5%), nausea, abdominal pain, and seizure (2% each). The most common adverse reactions occurring in 20 percent or more of patients who received TUKYSA were diarrhea, palmar-plantar erythrodysesthesia, nausea, fatigue, hepatotoxicity, vomiting, stomatitis, decreased appetite, abdominal pain, headache, anemia, and rash. Adverse reactions leading to treatment discontinuation occurred in 6 percent of patients who received TUKYSA; adverse reactions leading to treatment discontinuation of TUKYSA (in 1 percent or more of patients) were hepatotoxicity (1.5%) and diarrhea (1%).
The data were published in The New England Journal of Medicinein December 2019.
About TUKYSA (tucatinib)
TUKYSA is an oral medicine that is a tyrosine kinase inhibitor of the HER2 protein. In vitro (in lab studies), TUKYSA inhibited phosphorylation of HER2 and HER3, resulting in inhibition of downstream MAPK and AKT signaling and cell growth (proliferation), and showed anti-tumor activity in HER2-expressing tumor cells. In vivo (in living organisms), TUKYSA inhibited the growth of HER2-expressing tumors. The combination of TUKYSA and the anti-HER2 antibody trastuzumab showed increased anti-tumor activity in vitro and in vivo compared to either medicine alone.1
SeaGen Secure offers access and reimbursement support to help patients access TUKYSA. For more information, go to SeaGenSecure.com.
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 growth of cancer cells. An estimated 279,100 new cases of breast cancer will be diagnosed in the U.S. in 2020.3 Between 15 and 20 percent of breast cancer cases are HER2-positive.3 Historically, HER2-positive breast cancer tends to be more aggressive and more likely to recur than HER2-negative breast cancer.4,5,6 Up to 50 percent of metastatic HER2-positive breast cancer patients develop brain metastases over time.7,8,9
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. 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.
[1] TUKYSA [package insert]. Bothell, WA: Seattle Genetics, Inc.
[2] Anita Kulukian, Patrice Lee, Janelle Taylor, et al. Preclinical Activity of HER2-Selective Tyrosine Kinase Inhibitor Tucatinib as a Single Agent or in Combination with Trastuzumab or Docetaxel in Solid Tumor ModelsMol Cancer Ther 2020;19:976-987.
[3] Cancer Facts & Figures 2020. American Cancer Society website. https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2020/cancer-facts-and-figures-2020.pdf. Accessed March 10, 2020.
[3] Loibli S, Gianni L. HER2-positive breast cancer. Lancet. 2017; 389(10087): 2415-29.
[4] Slamon D, Clark G, Wong S, et al. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987; 235(4785): 177-82.
[5] Breast Cancer HER2 Status. American Cancer Society website. https://www.cancer.org/cancer/breast-cancer/understanding-a-breast-cancer-diagnosis/breast-cancer-her2-status.html. Accessed March 9, 2020.
[6] Freedman RA, Gelman RS, Anders CK, et al. TBCRC 022: a phase II trial of neratinib and capecitabine for patients with human epidermal growth factor receptor 2-positive breast cancer and brain metastases. J Clin Oncol. 2019;37:1081-1089.
[7] Olson EM, Najita JS, Sohl J, et al. Clinical outcomes and treatment practice patterns of patients with HER2-positive metastatic breast cancer in the post-trastuzumab era. Breast. 2013;22:525-531.
[8] Bendell JC, Domchek SM, Burstein HJ, et al. Central nervous system metastases in women who receive trastuzumab-based therapy for metastatic breast carcinoma. Cancer. 2003;97:2972-2977.
SOURCE: Seattle Genetics
Post Views: 119
