• 17 Dec 2020
• Admin
• News Article

Daiichi Sankyo Astrazeneca Initiate Tropion-Lung05 Phase 2 Trial Of Datopotamab Deruxtecan In Patients With Advanced/Metastatic Nsclc With Actionable

Daiichi Sankyo Company, Limited And Astrazeneca Announced The Initiation Of Tropion-Lung05, A Global Phase 2 Trial Of Datopotamab Deruxtecan (Dato-Dxd; Ds-1062), A Trop2 Directed Antibody Drug Conjugate (Adc), In Patients With Advanced Or Metastatic Non-Small Cell Lung Cancer (Nsclc) With Actionable Genomic Alterations Previously Treated With Kinase Inhibitor Therapy And Platinum-Based Chemotherapy With Or Without Immunotherapy.Targeted Therapy With Tyrosine Kinase Inhibitors (Tkis) Is Recommended As First-Line Or In Subsequent Lines Of Treatment In Patients With Advanced Or Metastatic Nsclc That Tests Positive For Certain Genomic Alterations As Tkis Offer Improved Response Rates Or Survival Compared To Traditional Chemotherapy. However, Once A Patient Develops Acquired Resistance To Tkis, Treatment Options Become More Limited.Trop2 Expression Has Been Associated With Poor Overall And Disease-Free Survival In Several Types Of Solid Tumors. Trop2 Expression Has Been Observed In The Majority Of Adenocarcinoma And Squamous Cell Carcinoma Nsclc. There Are No Trop2 Directed Therapies Or Adcs Currently Approved For The Treatment Of Nsclc.&Ldquo;Following Preliminary Findings Of Durable Responses Observed In Tropion-Pantumor01, The Ongoing Phase 1 Trial Of Datopotamab Deruxtecan In Non-Small Cell Lung Cancer, We Will Evaluate Whether Targeting Trop2 With Our Dxd Adc Technology Could Be A New Treatment Strategy For Patients With Previously Treated Advanced Or Metastatic Non-Small Cell Lung Cancer With Actionable Genomic Alterations,&Rdquo; Said Gilles Gallant, Bpharm, Phd, Fopq, Senior Vice President, Global Head, Oncology Development, Oncology R&Amp;D, Daiichi Sankyo.&Ldquo;Many Patients With Nsclc Will Ultimately Develop Resistance To Available Targeted Therapies, And Treatment Options For Advanced Nsclc Are Limited,&Rdquo; Said Cristian Massacesi, Senior Vice President, Head Of Late Stage Development Oncology R&Amp;D, Astrazeneca. &Ldquo;Tropion-Lung05 Provides An Opportunity To Evaluate Datopotamab Deruxtecan, A Targeted Adc Approach With Promise In This Patient Population.&Rdquo;The Global, Multicenter, Single-Arm, Open-Label Phase 2 Study Will Evaluate The Efficacy And Safety Of Datopotamab Deruxtecan (6.0 Mg/Kg) In Patients With Advanced Or Metastatic Nsclc With Actionable Genomic Alterations With Progression On Or After At Least One Tyrosine Kinase Inhibitor And At Least One Regimen Of Platinum-Based Chemotherapy (With Or Without Other Systemic Therapies). Patients With One Or More Genomic Alterations Including Egfr, Alk, Ros1, Ntrk, Braf, Ret, Or Met Exon 14 Skipping Who Received Up To Four Prior Lines Of Treatment Are Eligible For The Study.Lung Cancer Is The Most Common Cancer And The Leading Cause Of Cancer Mortality Worldwide; There Were An Estimated 2.1 Million New Cases Of Lung Cancer In 2018 And 1.8 Million Deaths. Nsclc Accounts For 80 To 85 Percent Of All Lung Cancers.A Number Of Targeted Tyrosine Kinase Inhibitors, Which Offer Improved Survival Rates Over Traditional Chemotherapy Regimens, Are Approved For Treatment Of Nsclc With Specific Genomic Alterations. The Most Common Alterations For Which Kinase Inhibitors Are Approved Are Egfr (Approximately 10 To 35% Frequency) And Alk Rearrangement (Approximately 3 To 7%). All Patients Eventually Develop Resistance To Available Therapies.Trop2 (Trophoblast Cell-Surface Antigen 2) Is A Transmembrane Glycoprotein That Is Overexpressed In Many Cancers. Trop2 Expression Has Been Associated With Poor Overall And Disease-Free Survival In Several Types Of Solid Tumors. Trop2 Expression Has Been Observed In Up To 64% Of Adenocarcinoma And Up To 75% Of Squamous Cell Carcinoma Nsclc. There Are No Trop2 Directed Therapies Or Adcs Currently Approved For The Treatment Of Nsclc.Adcs Are Targeted Cancer Medicines That Deliver Cytotoxic Chemotherapy (Payload) To Cancer Cells Via A Linker Attached To A Monoclonal Antibody That Binds To A Specific Target Expressed On Cancer Cells. Designed Using Daiichi Sankyo&Rsquo;S Proprietary Dxd Adc Technology, Datopotamab Deruxtecan Is Comprised Of A Humanized Anti-Trop2 Igg13 Monoclonal Antibody Attached To A Topoisomerase I Inhibitor Payload, An Exatecan Derivative, Via A Tetrapeptide-Based Cleavable Linker With A Drug-To-Antibody Ratio (Dar) Of Four.