XALKORI is the First Tyrosine Kinase Inhibitor to Receive Breakthrough Designation for the Treatment of Patients with Previously-treated Metastatic Non-Small Cell Lung Cancer with MET Exon 14 Alterations
Additional Breakthrough Therapy Designation for the Treatment of Patients with Relapsed or Refractory Systemic Anaplastic Large Cell Lymphoma that is ALK-positive
NEW YORK, NY, USA I May 29, 2018 I Pfizer Inc. (NYSE:PFE) announced today that the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy designation for XALKORI® (crizotinib) for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with MET exon 14 alterations with disease progression on or after platinum-based chemotherapy. The FDA also granted Breakthrough Therapy designation for XALKORI for the treatment of patients with relapsed or refractory systemic anaplastic large cell lymphoma (ALCL) that is anaplastic lymphoma kinase (ALK)-positive.
MET is a transmembrane tyrosine receptor kinase which is expressed in several types of cells. In patients with NSCLC, MET exon 14 alterations occur in approximately three percent of NSCLC tumors.1 Anaplastic large cell lymphoma is a rare type of non-Hodgkin lymphoma, divided into ALK-positive or ALK-negative disease.2,3 Despite the activity of chemotherapy, many patients with ALCL relapse or require alternative treatment approaches.4
“Biomarker-driven therapies have changed the way we treat cancer, helping to ensure that patients receive the right medicine for their disease,” said Mace Rothenberg, M.D., chief development officer, Oncology, Pfizer Global Product Development. “These Breakthrough Therapy designations for XALKORI exemplify our commitment to precision medicine development and delivering medicines that have the potential to transform the lives of patients whose cancers carry these genomic alterations.”
XALKORI is currently approved in the U.S. for the treatment of patients with metastatic NSCLC whose tumors are ALK-positive or ROS1-positive as detected by an FDA-approved test. XALKORI became a first-line standard of care for ALK-positive metastatic NSCLC in its first approved indication and has proven to be a practice-changing treatment for patients with ALK-positive and ROS1-positive NSCLC, globally. It is the only FDA-approved treatment indicated for both ALK-positive and ROS1-positive metastatic NSCLC. If approved in patients with metastatic NSCLC with MET exon 14 alterations, XALKORI will be the only TKI with demonstrated efficacy in three separate biomarker-driven indications in NSCLC.
The Breakthrough Therapy designation for patients with metastatic NSCLC with MET exon 14 alterations was supported by results from an expansion cohort of the Phase 1 PROFILE 1001 study, in which XALKORI showed antitumor activity.5
The designation for patients with relapsed or refractory systemic ALCL that is ALK-positive was supported by the results from Study ADVL0912 (NCT00939770) and Study A8081013 (NCT01121588). Study ADVL0912 is a Phase 1/2 study conducted by the Children’s Oncology Group evaluating the maximum dose that is safe and tolerable, and assessing preliminary clinical activity in pediatric patients with relapsed or refractory solid tumors and ALCL. Study A8081013 evaluated XALKORI in pediatric and adult patients with advanced malignancies known to be ALK-positive other than NSCLC and included patients with relapsed/refractory ALCL. These two studies showed compelling antitumor activity in pediatric and adult patients who received XALKORI.6,7
Please visit clinicaltrials.gov for more information on these studies.
The FDA’s Breakthrough Therapy designation is intended to expedite the development and review of a medicine if it is intended to treat a serious or life-threatening disease and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies. The Breakthrough Therapy designation is distinct from the FDA’s other mechanisms to expedite drug development and review.8
About MET Alterations in Non-Small Cell Lung Cancer
Lung cancer is the leading cause of cancer deaths worldwide.9 NSCLC accounts for about 85 percent of lung cancer cases and remains difficult to treat, particularly in the metastatic setting.10 Approximately 75 percent of NSCLC patients are diagnosed late with metastatic or advanced disease where the five-year survival rate is only five percent.11,12
MET is a transmembrane tyrosine receptor kinase which is expressed in several types of cells. In patients with NSCLC, MET exon 14 alterations occur in approximately three percent of NSCLC tumors.1
About Anaplastic Large Cell Lymphoma
Anaplastic large cell lymphoma (ALCL) is a rare type of non-Hodgkin lymphoma (NHL), but one of the more common subtypes of T-cell lymphoma. ALCL comprises about two percent of all NHLs and approximately 20 percent of all T-cell lymphomas.2,3 Patients with systemic ALCL are divided into two groups, ALK-positive or ALK-negative. Both of these lymphomas are treated as aggressive (fast-growing) lymphomas, yet many patients still relapse or require alternative treatment approaches. ALK-positive ALCL usually affects children and young adults.4
About XALKORI® (crizotinib)
XALKORI is a tyrosine kinase inhibitor (TKI) indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK) or ROS1-positive as detected by an FDA-approved test. XALKORI has received approval for patients with ALK-positive NSCLC in more than 90 countries including Australia, Canada, China, Japan, South Korea and the European Union. XALKORI is also approved for ROS1-positive NSCLC in more than 60 countries.
About Pfizer in Lung Cancer
Pfizer Oncology is committed to addressing the unmet needs of patients with lung cancer, the leading cause of cancer-related deaths worldwide and a particularly difficult-to-treat disease. Pfizer strives to address the diverse and evolving needs of patients with non-small cell lung cancer (NSCLC) by developing efficacious and tolerable therapies, including biomarker-driven therapies and immuno-oncology (IO) agents and combinations. By combining leading scientific insights with a patient-centric approach, Pfizer is continually advancing its work to match the right patient with the right medicine at the right time. Through our growing research pipeline and collaboration efforts, we are committed to delivering renewed hope to patients living with NSCLC.
About Pfizer Oncology
Pfizer Oncology is committed to pursuing innovative treatments that have a meaningful impact on people living with cancer. Our growing pipeline of biologics, small molecules, and immunotherapies is focused on identifying and translating the best scientific breakthroughs into clinical application for patients across a diverse array of solid tumors and hematologic cancers. Today, we have 10 approved oncology medicines and 14 assets currently in clinical development. By maximizing our internal scientific resources and collaborating with other companies, government and academic institutions, as well as patients and non-profit and professional organizations, we are bringing together the brightest and most enterprising minds to take on the toughest cancers. Together we can accelerate breakthrough treatments to patients around the world and work to redefine life with cancer.
Pfizer Inc.: Working together for a healthier world®
At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development and manufacture of health care products. Our global portfolio includes medicines and vaccines as well as many of the world’s best-known consumer health care products. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world’s premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For more than 150 years, we have worked to make a difference for all who rely on us. We routinely post information that may be important to investors on our website at www.pfizer.com. In addition, to learn more, please visit us on www.pfizer.com and follow us on Twitter at @Pfizer and @Pfizer_News, LinkedIn, YouTube, and like us on Facebook at Facebook.com/Pfizer.
1 Lovly, C., P. Paik. 2017. MET Exon 14 Skipping Mutations in Lung Cancer. My Cancer Genome https://www.mycancergenome.org/content/disease/lung-cancer/met/343/. (Updated June 15). Accessed May 2018.
2 Ward E, DeSantis C, Robbins A, et al. Childhood and adolescent cancer statistics, 2014. CA Cancer J Clin 2014;64(2):83-103.
3 Drexler HG, Gignac SM, von Wasielewski R, et al. Pathobiology of NPM-ALK and variant fusion genes in anaplastic large cell lymphoma and other lymphomas. Leukemia 2000;14:1533–59.
4 Lymphoma Research Foundation. Getting the Facts. Anaplastic Large Cell Lymphoma. https://www.lymphoma.org/wp-content/uploads/2018/04/LRF_FACTSHEET_ANAPLASTIC_LARGE_CELL_LYMPHOMA.pdf. Accessed May 2018.
5 Efficacy and safety of crizotinib in patients (pts) with advanced MET exon 14-altered non-small cell lung cancer (NSCLC). Alexander E. Drilon et al. Journal of Clinical Oncology 2016 34:15_suppl, 108-108
6 Gambacorti-Passerini C, Orlov S, Zhang L, et al. Long-term effects of crizotinib in ALK-positive tumors (excluding NSCLC): A phase 1b open-label study. Am J Hematol. 2018;93:607–614.
7 P. Mossé, Yael & D. Voss, Stephan & S. Lim, Megan & Rolland, Delphine & Minard, Charles & Fox, Elizabeth & Adamson, Peter & Wilner, Keith & Blaney, Susan & J. Weigel, Brenda. (2017). Targeting ALK With Crizotinib in Pediatric Anaplastic Large Cell Lymphoma and Inflammatory Myofibroblastic Tumor: A Children’s Oncology Group Study. Journal of Clinical Oncology. 35. JCO.2017.73.483.
8 U.S. Food and Drug Administration Fact Sheet: Breakthrough Therapies. Available at: https://www.fda.gov/RegulatoryInformation/LawsEnforcedbyFDA/SignificantAmendmentstotheFDCAct/FDASIA/ucm329491.htm. Accessed May 2018.
9 The International Agency for Research on Cancer, the World Health Organization. GLOBOCAN 2008. Available at: http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx (select “Lung” from the drop-down menu). Accessed May 2018.
10 Reade CA, Ganti AK. EGFR targeted therapy in non-small cell lung cancer: potential role of cetuximab. Biologics. 2009; 3: 215–224.
11 Yang P, Allen MS, Aubry MC, et al. Clinical features of 5,628 primary lung cancer patients: experience at Mayo Clinic from 1997 to 2003. Chest. 2005;128(1):452–462.
12 American Cancer Society. Detailed Guide: Lung Cancer (Non-Small Cell). Available at: http://www.cancer.org/cancer/lungcancer-non-smallcell/detailedguide/non-small-cell-lung-cancer-survival-rates. Accessed May 2018.
SOURCE: Pfizer
Post Views: 28
XALKORI is the First Tyrosine Kinase Inhibitor to Receive Breakthrough Designation for the Treatment of Patients with Previously-treated Metastatic Non-Small Cell Lung Cancer with MET Exon 14 Alterations
Additional Breakthrough Therapy Designation for the Treatment of Patients with Relapsed or Refractory Systemic Anaplastic Large Cell Lymphoma that is ALK-positive
NEW YORK, NY, USA I May 29, 2018 I Pfizer Inc. (NYSE:PFE) announced today that the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy designation for XALKORI® (crizotinib) for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with MET exon 14 alterations with disease progression on or after platinum-based chemotherapy. The FDA also granted Breakthrough Therapy designation for XALKORI for the treatment of patients with relapsed or refractory systemic anaplastic large cell lymphoma (ALCL) that is anaplastic lymphoma kinase (ALK)-positive.
MET is a transmembrane tyrosine receptor kinase which is expressed in several types of cells. In patients with NSCLC, MET exon 14 alterations occur in approximately three percent of NSCLC tumors.1 Anaplastic large cell lymphoma is a rare type of non-Hodgkin lymphoma, divided into ALK-positive or ALK-negative disease.2,3 Despite the activity of chemotherapy, many patients with ALCL relapse or require alternative treatment approaches.4
“Biomarker-driven therapies have changed the way we treat cancer, helping to ensure that patients receive the right medicine for their disease,” said Mace Rothenberg, M.D., chief development officer, Oncology, Pfizer Global Product Development. “These Breakthrough Therapy designations for XALKORI exemplify our commitment to precision medicine development and delivering medicines that have the potential to transform the lives of patients whose cancers carry these genomic alterations.”
XALKORI is currently approved in the U.S. for the treatment of patients with metastatic NSCLC whose tumors are ALK-positive or ROS1-positive as detected by an FDA-approved test. XALKORI became a first-line standard of care for ALK-positive metastatic NSCLC in its first approved indication and has proven to be a practice-changing treatment for patients with ALK-positive and ROS1-positive NSCLC, globally. It is the only FDA-approved treatment indicated for both ALK-positive and ROS1-positive metastatic NSCLC. If approved in patients with metastatic NSCLC with MET exon 14 alterations, XALKORI will be the only TKI with demonstrated efficacy in three separate biomarker-driven indications in NSCLC.
The Breakthrough Therapy designation for patients with metastatic NSCLC with MET exon 14 alterations was supported by results from an expansion cohort of the Phase 1 PROFILE 1001 study, in which XALKORI showed antitumor activity.5
The designation for patients with relapsed or refractory systemic ALCL that is ALK-positive was supported by the results from Study ADVL0912 (NCT00939770) and Study A8081013 (NCT01121588). Study ADVL0912 is a Phase 1/2 study conducted by the Children’s Oncology Group evaluating the maximum dose that is safe and tolerable, and assessing preliminary clinical activity in pediatric patients with relapsed or refractory solid tumors and ALCL. Study A8081013 evaluated XALKORI in pediatric and adult patients with advanced malignancies known to be ALK-positive other than NSCLC and included patients with relapsed/refractory ALCL. These two studies showed compelling antitumor activity in pediatric and adult patients who received XALKORI.6,7
Please visit clinicaltrials.gov for more information on these studies.
The FDA’s Breakthrough Therapy designation is intended to expedite the development and review of a medicine if it is intended to treat a serious or life-threatening disease and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies. The Breakthrough Therapy designation is distinct from the FDA’s other mechanisms to expedite drug development and review.8
About MET Alterations in Non-Small Cell Lung Cancer
Lung cancer is the leading cause of cancer deaths worldwide.9 NSCLC accounts for about 85 percent of lung cancer cases and remains difficult to treat, particularly in the metastatic setting.10 Approximately 75 percent of NSCLC patients are diagnosed late with metastatic or advanced disease where the five-year survival rate is only five percent.11,12
MET is a transmembrane tyrosine receptor kinase which is expressed in several types of cells. In patients with NSCLC, MET exon 14 alterations occur in approximately three percent of NSCLC tumors.1
About Anaplastic Large Cell Lymphoma
Anaplastic large cell lymphoma (ALCL) is a rare type of non-Hodgkin lymphoma (NHL), but one of the more common subtypes of T-cell lymphoma. ALCL comprises about two percent of all NHLs and approximately 20 percent of all T-cell lymphomas.2,3 Patients with systemic ALCL are divided into two groups, ALK-positive or ALK-negative. Both of these lymphomas are treated as aggressive (fast-growing) lymphomas, yet many patients still relapse or require alternative treatment approaches. ALK-positive ALCL usually affects children and young adults.4
About XALKORI® (crizotinib)
XALKORI is a tyrosine kinase inhibitor (TKI) indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK) or ROS1-positive as detected by an FDA-approved test. XALKORI has received approval for patients with ALK-positive NSCLC in more than 90 countries including Australia, Canada, China, Japan, South Korea and the European Union. XALKORI is also approved for ROS1-positive NSCLC in more than 60 countries.
About Pfizer in Lung Cancer
Pfizer Oncology is committed to addressing the unmet needs of patients with lung cancer, the leading cause of cancer-related deaths worldwide and a particularly difficult-to-treat disease. Pfizer strives to address the diverse and evolving needs of patients with non-small cell lung cancer (NSCLC) by developing efficacious and tolerable therapies, including biomarker-driven therapies and immuno-oncology (IO) agents and combinations. By combining leading scientific insights with a patient-centric approach, Pfizer is continually advancing its work to match the right patient with the right medicine at the right time. Through our growing research pipeline and collaboration efforts, we are committed to delivering renewed hope to patients living with NSCLC.
About Pfizer Oncology
Pfizer Oncology is committed to pursuing innovative treatments that have a meaningful impact on people living with cancer. Our growing pipeline of biologics, small molecules, and immunotherapies is focused on identifying and translating the best scientific breakthroughs into clinical application for patients across a diverse array of solid tumors and hematologic cancers. Today, we have 10 approved oncology medicines and 14 assets currently in clinical development. By maximizing our internal scientific resources and collaborating with other companies, government and academic institutions, as well as patients and non-profit and professional organizations, we are bringing together the brightest and most enterprising minds to take on the toughest cancers. Together we can accelerate breakthrough treatments to patients around the world and work to redefine life with cancer.
Pfizer Inc.: Working together for a healthier world®
At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development and manufacture of health care products. Our global portfolio includes medicines and vaccines as well as many of the world’s best-known consumer health care products. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world’s premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For more than 150 years, we have worked to make a difference for all who rely on us. We routinely post information that may be important to investors on our website at www.pfizer.com. In addition, to learn more, please visit us on www.pfizer.com and follow us on Twitter at @Pfizer and @Pfizer_News, LinkedIn, YouTube, and like us on Facebook at Facebook.com/Pfizer.
1 Lovly, C., P. Paik. 2017. MET Exon 14 Skipping Mutations in Lung Cancer. My Cancer Genome https://www.mycancergenome.org/content/disease/lung-cancer/met/343/. (Updated June 15). Accessed May 2018.
2 Ward E, DeSantis C, Robbins A, et al. Childhood and adolescent cancer statistics, 2014. CA Cancer J Clin 2014;64(2):83-103.
3 Drexler HG, Gignac SM, von Wasielewski R, et al. Pathobiology of NPM-ALK and variant fusion genes in anaplastic large cell lymphoma and other lymphomas. Leukemia 2000;14:1533–59.
4 Lymphoma Research Foundation. Getting the Facts. Anaplastic Large Cell Lymphoma. https://www.lymphoma.org/wp-content/uploads/2018/04/LRF_FACTSHEET_ANAPLASTIC_LARGE_CELL_LYMPHOMA.pdf. Accessed May 2018.
5 Efficacy and safety of crizotinib in patients (pts) with advanced MET exon 14-altered non-small cell lung cancer (NSCLC). Alexander E. Drilon et al. Journal of Clinical Oncology 2016 34:15_suppl, 108-108
6 Gambacorti-Passerini C, Orlov S, Zhang L, et al. Long-term effects of crizotinib in ALK-positive tumors (excluding NSCLC): A phase 1b open-label study. Am J Hematol. 2018;93:607–614.
7 P. Mossé, Yael & D. Voss, Stephan & S. Lim, Megan & Rolland, Delphine & Minard, Charles & Fox, Elizabeth & Adamson, Peter & Wilner, Keith & Blaney, Susan & J. Weigel, Brenda. (2017). Targeting ALK With Crizotinib in Pediatric Anaplastic Large Cell Lymphoma and Inflammatory Myofibroblastic Tumor: A Children’s Oncology Group Study. Journal of Clinical Oncology. 35. JCO.2017.73.483.
8 U.S. Food and Drug Administration Fact Sheet: Breakthrough Therapies. Available at: https://www.fda.gov/RegulatoryInformation/LawsEnforcedbyFDA/SignificantAmendmentstotheFDCAct/FDASIA/ucm329491.htm. Accessed May 2018.
9 The International Agency for Research on Cancer, the World Health Organization. GLOBOCAN 2008. Available at: http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx (select “Lung” from the drop-down menu). Accessed May 2018.
10 Reade CA, Ganti AK. EGFR targeted therapy in non-small cell lung cancer: potential role of cetuximab. Biologics. 2009; 3: 215–224.
11 Yang P, Allen MS, Aubry MC, et al. Clinical features of 5,628 primary lung cancer patients: experience at Mayo Clinic from 1997 to 2003. Chest. 2005;128(1):452–462.
12 American Cancer Society. Detailed Guide: Lung Cancer (Non-Small Cell). Available at: http://www.cancer.org/cancer/lungcancer-non-smallcell/detailedguide/non-small-cell-lung-cancer-survival-rates. Accessed May 2018.
SOURCE: Pfizer
Post Views: 28
