Study of DS-1062a Versus Docetaxel in Previously Treated Advanced or Metastatic Non-small Cell Lung Cancer With or Without Actionable Genomic Alterations (TROPION-LUNG01)

Phase 3 Randomized Study of DS-1062a Versus Docetaxel in Previously Treated Advanced or Metastatic Non-Small Cell Lung Cancer (TROPION-LUNG01)

This study will evaluate the efficacy, safety, and pharmacokinetics of DS-1062a versus docetaxel in participants with previously treated advanced or metastatic non-small cell lung cancer (NSCLC) with or without actionable genomic alterations.

Study Overview

• Status: Active, not recruiting
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: DS-1062a; Drug: Docetaxel

Detailed Description

This study will evaluate DS-1062a 6.0 mg/kg vs docetaxel 75 mg/m^2 in participants with advanced or metastatic NSCLC with or without actionable genomic alterations (AGAs). Participants without actionable genomic alterations must have been previously treated with platinum-based chemotherapy and α (anti)-programmed cell death 1 (PD-1)/α-programmed cell death ligand 1 (PD-L1) monoclonal antibody, either in combination or sequentially. Participants with AGA must have progressed on or after 1 platinum-containing therapy and 1 to 2 prior lines of approved targeted therapy for the applicable genomic alteration. The study will be divided into 3 periods: Screening Period, Treatment Period, and Follow-up Period.

• Study Type: Interventional
• Enrollment (Estimated): 590
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, 01878
    • CER San Juan
  • Pergamino, Argentina, B2700CPM
    • Centro de Investigacion Pergamino S.A.
  • Rosario, Argentina, S2000KZE
    • Instituto de OncologÃÂ-a de Rosario
  • Rosario, Argentina, S2000
    • Gaston Martinengo
• Australia
  • Bedford Park, Australia, 05042
    • Flinders Medical Centre
  • Blacktown, Australia, 02148
    • Blacktown Hosital
  • Heidelberg, Australia, 03084
    • Austin Hospital
  • North Ryde, Australia, 02109
    • Macquarie Hospital
  • Sydney, Australia, 2145
    • Crown Princess Mary Cancer Centre Westmead Hospital
  • Wollongong, Australia, 02500
    • Southern Medical Day Care Centre
• Belgium
  • Haine-Saint-Paul, Belgium, 07100
    • Centre Hospitalier Jolimont-Lobbes
  • Libramont, Belgium, B-6800
    • CHA Centre Hospitalier de l Ardenne
  • Liège, Belgium, 04000
    • CHR site de la Citadelle
  • Yvoir, Belgium, 05530
    • Chu Ucl Namur
• Brazil
  • Fortaleza, Brazil, 60430-230
    • Instituto do Cancer do Ceara - ICC
  • Porto Alegre, Brazil, 90610-000
    • Hospital Sao Lucas da PUCRS
  • Porto Alegre, Brazil, 91350-200
    • Hospital Nossa Senhora da Conceicao
  • Rio De Janeiro, Brazil, 20231-050
    • Instituto Nacional de Cancer-INCA
  • São José Do Rio Preto, Brazil, 15090-000
    • Hospital de Base de São José do Rio Preto
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute
  • Ontario
    • Toronto, Ontario, Canada, M5G0A3
      • University Health Network - Princess Margaret Hospital
    • Toronto, Ontario, Canada, ON M4N 3M5
      • Sunnbrook Health Sciences Centre
  • Quebec
    • Montréal, Quebec, Canada, H4A 3J1
      • MUHC-Glen Site and MUHC Research Institute
• China
  • Beijing, China, 100142
    • Beijing Cancer Hospital
  • Hangzhou, China, 310003
    • Linyi Cancer Hospital
  • Hangzou, China, 310022
    • The First Affiliated Hospital of Zhejiang University
  • Heilongjiang, China, 150081
    • Harbin Medical University Cancer Hospital
  • Heilongjiang, China, 154007
    • Jiamusi Cancer Tuberculosis Hospital
  • Henan, China, 450008
    • Fudan University Shanghai Cancer Center
  • Hubei, China, 430079
    • Hubei Cancer Hospital
  • Shandong, China, 276000
    • The First Affiliated Hospital of Xi'an Jiaotong University
  • Shanghai, China
    • Shanghai Chest Hospital
  • Shanghai Sheng, China, 200032
    • Henan Cancer Hospital
  • Shanxi, China, 710061
    • Zhejiang Cancer Hospital
  • Sichuan Province, China
    • West China Hospital, Sichuan University
  • Tianjin, China, 300060
    • Tianjin Medical University Cancer Institute and Hospital
  • Wuhan, China, 43002
    • Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology
  • Zhejiang, China, 310016
    • Sir Run Run Shaw Hospital Zhejiang University School of Medicine
• Czechia
  • Praha, Czechia, 12800
    • Vseobecna Fakultni Nemocnice VFN
• France
  • Besançon, France, 25030
    • Hôpital Jean Minjoz
  • Grenoble, France, 38043
    • Centre Hospitalier Universitaire de Grenoble
  • Lyon, France, 69008
    • Centre Léon Bérard
  • Lyon, France
    • CHU Louis Pradel
  • Marseille, France, 13915
    • APHM - Hôpital Nord
  • Nantes, France, 44000
    • University Hospital of Nantes - Thoracic Oncology
  • Paris, France, 75248
    • Institut Curie
  • Poitiers, France, 86000
    • CHU de Poitier Pole Regional de Cancerologie
  • Rennes, France, 35000
    • Hôpital Pontchaillou
  • Strasbourg, France, 67098
    • Hopitaux Universitaire de Strasbourg
  • Sureesnes, France, 92150
    • Hopital Foch
  • Toulouse, France, 31059
    • CHU Toulouse Hopital Larrey
  • Villejuif, France, 94805
    • Gustav Roussy Cancer Campus Grand Paris
• Germany
  • Berlin, Germany, 13125
    • Evangelische Lungenklinik Berlin
  • Berlin, Germany, 10117
    • Charite - Universitaetsmedizin Berlin
  • Frankfurt am main, Germany, 60488
    • IKF Krankenhaus Nordwest
  • Freiburg, Germany, 79106
    • Universitaetsklinikum Freiburg
  • Gauting, Germany, 82131
    • Asklepios Fachklinik Muenchen-Gauting
  • Heidelberg, Germany, 69126
    • Thoraxklinik Heidelberg gGmbH
  • Hemer, Germany, 58675
    • Lungenklinik Hemer
  • Kempten, Germany, 87439
    • Klinikverbund Allgäu
  • Koeln, Germany, 50937
    • Universitaet zu Koeln - Uniklinik Koeln
  • Standort Gießen, Germany
    • Medizinische Klinik V
  • Traunstein, Germany
    • Klinikum Traunstein
• Hong Kong
  • Hong Kong, Hong Kong, 999077
    • Queen Mary Hospital
  • Hong Kong, Hong Kong, 99999
    • Prince of Wales Hospital / The Chinese University of Hong Kong
• Hungary
  • Budapest, Hungary, 1145
    • Uzsoki Utcai Kórház
  • Budapest, Hungary, 01121
    • Orszagos Koranyi TBC es Pulmonologiai Intezet
  • Tatabánya, Hungary, 02800
    • Szent Borbala Korhaz
  • Tolna, Hungary
    • Tolna Megyei Balassa János Kórház
  • Torokbalint, Hungary, H-2045
    • Tudogyogyintezet Torokbalint
• Italy
  • Bologna, Italy, 40138
    • Azienda Ospedaliero- Universitaria Policlinico S. Orsola-Malpighi
  • Catania, Italy, 95030
    • Azienda Ospedaliera Universitaria Policlinico G Rodolico San Marco
  • Genova, Italy, 16149
    • ASL 3 Genovese Oncologia Medica Villa Scassi
  • Milan, Italy, 20133
    • Fondazione IRCCS Istituto Nazionale Tumori
  • Milano, Italy, 20141
    • IRCCS Istituto Europeo di Oncologia
  • Milano, Italy, 20122
    • Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
  • Orbassano, Italy, 10043
    • Azienda Ospedaliero-Universitaria San Luigi Gonzaga
  • Roma, Italy, 00168
    • Fondazione Policlinico Universitario Agostino Gemelli IRCCS
  • Roma, Italy, RM00144
    • Instituicao de Fisioterapeutas Ocupacionais
• Japan
  • Akashi, Japan, 673-8558
    • Hyogo Cancer Center
  • Chuo Ku, Japan, 951-8566
    • Niigata Cancer Center Hospital
  • Fukuoka, Japan, 812-8582
    • Kyushu University Hospital
  • Hidaka, Japan, 350-1298
    • Saitama Medical University International Medical Center
  • Hirakata, Japan, 573-1191
    • Kansai Medical University Hospital
  • Kanazawa, Japan, 920-8641
    • Kanazawa University Hospital
  • Kashiwa, Japan, 277-8577
    • National Cancer Center Hospital East
  • Koto-Ku, Japan, 135-8550
    • The Cancer Institute Hospital of JFCR
  • Kyoto, Japan, 606-8507
    • Kyoto University Hospital
  • Matsuyama, Japan, 791-0280
    • NHO Shikoku Cancer Center
  • Nagaizumi-chō, Japan, 411-8777
    • Shizuoka Cancer Center
  • Okayama, Japan, 36927
    • Okayama University Hospital
  • Osaka, Japan, 541-8567
    • Osaka International Cancer Institute
  • Osaka-shi, Japan, 534-0021
    • Osaka City General Hospital
  • Saitama, Japan, 362-0806
    • Saitama Cancer Center
  • Sendai-shi, Japan, 980-0873
    • Sendai Kousei Hospital
  • Shiroishi, Japan, 003-0804
    • Nho Hokkaido Cancer Center
  • Tokushima, Japan, 770-8503
    • Tokushima University Hospital
  • Tokyo, Japan, 104-0045
    • National Cancer Center Hospital
  • Toyoake, Japan, 470-1192
    • Fujita Health University Hospital
  • Ōsaka-sayama, Japan, 589-8511
    • Kindai University Hospital
• Korea, Republic of
  • Cheongju-si, Korea, Republic of, 28644
    • Chungbuk National University Hospital
  • Daegu, Korea, Republic of, 41404
    • Kyungpook National University Chilgok Hospital
  • Gyeonggi-do, Korea, Republic of, 16247
    • St. Vincents Hospital The Catholic University of Korea
  • Seongnam-si, Korea, Republic of, 13620
    • Seoul National University Bundang Hospital
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 03181
    • Kangbuk Samsung Hospital
  • Seoul, Korea, Republic of, 07061
    • Seoul National University Boramae Medical Center
  • Seoul, Korea, Republic of, 03722
    • Yonsei University Health System - Severance Hospital
  • Seoul, Korea, Republic of, 06591
    • The Catholic University of Korea, Seoul St. Marys Hospital
• Mexico
  • Aguascalientes, Mexico, 20230
    • San Peregrino Cancer Center
  • Ciudad de mexico, Mexico, 14050
    • Hospital Medica Sur Tlalpan
  • Guadalajara, Mexico, 44280
    • Hospital Civil de Guadalajara Fray Antonio Alcalde
  • Monterrey, Mexico, 64460
    • Hospital Universitario Jose Eleuterio Gonzalez
• Netherlands
  • Amsterdam, Netherlands, 3000 CA
    • Erasmus MC
  • Breda, Netherlands, 4818 CK
    • Amphia ziekenhuis
  • Harderwijk, Netherlands, 3844 DG
    • Isala Klinieken
  • Rotterdam, Netherlands, 3015 CD
    • St. Jansdal Ziekenhuis
• Poland
  • Białystok, Poland, 15-276
    • II Klinika Chorob Pluc i Gruzlicy
  • Gdynia, Poland, 81-519
    • Szpitale Pomorskie Sp.zo.o
  • Lublin, Poland, 20-090
    • Ms Pneumed
  • Olsztyn, Poland, 10-357
    • SP Zespol Gruzlicy i Chorob Pluc
  • Poznań, Poland, 60-693
    • Med Polonia Sp. z o.o.
  • Prabuty, Poland, 82-550
    • Szpital Specjalistyczny w Prabutach Sp. z o.o.
  • Słupsk, Poland, 76-200
    • Oddział Onkologii Wojewódzki Szpital Specjalistyczny Słupsk
  • Warsaw, Poland, 02-781
    • Maria Sklodowska-Curie National Research Institute of Oncology
  • Warsaw, Poland, 01-748
    • Magodent Sp. z.o.o Szpital Elblaska
• Puerto Rico
  • San Juan, Puerto Rico, 00927
    • FDI Clinical Research
• Romania
  • Baia Mare, Romania, 430291
    • SC Oncopremium Team SRL
  • Bucharest, Romania, 20125
    • Centrul Medical Sanador
  • Bucuresti, Romania, 022328
    • Institutul Oncologic Profesor Doctor Alexandru Trestioreanu
  • Constanţa, Romania, 900591
    • Clinical Emergency Hospital
  • Craiova, Romania, 200385
    • Oncolab SRL
  • Craiova, Romania, 200103
    • Onco Clinic Consult SA
  • Craiova, Romania, 200347
    • Sf Nectarie Oncology Center
  • Timişoara, Romania, 300425
    • SC Oncomed SRL
• Russian Federation
  • Kursk, Russian Federation, 305524
    • Kursk Regional Clinical Oncology Dispensary
  • Moscow, Russian Federation, 115478
    • Federal State Budgetary Institution - N.N. Blokhin National Medical Research Center of Oncology
  • Moscow, Russian Federation, 121467
    • University Headache Clinic LLC
  • Moscow, Russian Federation, 129515
    • VitaMed LLC
  • Moscow, Russian Federation
    • Institute of Oncology Hadassah Moscow
  • Novosibirsk, Russian Federation, 630099
    • LLC MSCH "Klinitsist"
  • Saint Petersburg, Russian Federation, 197758
    • N.N. Petrov Research Institute of Oncology
• Singapore
  • Singapore, Singapore, 169610
    • National Cancer Centre Singapore
  • Singapore, Singapore, 217562
    • ICON Cancer Centre Farrer Park Hospital
  • Singapore, Singapore, 258499
    • OncoCare Cancer Centre - Gleneagles Medical Centre Location
• Spain
  • Barcelona, Spain, 08025
    • Hospital de la Santa Creu i Sant Pau
  • Barcelona, Spain, 08036
    • Hospital Clínic i Provincial de Barcelona
  • Barcelona, Spain, 80350
    • Hospital Universitario Vall d'Hebron
  • Madrid, Spain, 28040
    • Hospital Universitario Fundacion Jimenez Diaz
  • Madrid, Spain, 28041
    • Hospital Universitario 12 De Octubre
  • Madrid, Spain, 28222
    • Hospital Puerte de Hierro de Majadahonda
  • Málaga, Spain, 29010
    • Hospital Regional Universitario Malaga
  • Ourense, Spain, 32005
    • CHUO
  • Sevilla, Spain, 41007
    • Hospital Virgen Macarena
  • Sevilla, Spain, 41014
    • Hospital Universitario de Valme
  • Valencia, Spain, 46026
    • Hospital Universitari I Politecnic La Fe
  • Valencia, Spain, 46014
    • Hospital General Universitario de Valencia
  • Zaragoza, Spain, 50009
    • Hospital Clínico Universitario Lozano Bleza
• Switzerland
  • Bern, Switzerland, 3010
    • Inselspital Universitätsspital Bern
  • Saint Gallen, Switzerland, 9007
    • Kantonsspital St. Gallen
  • Zürich, Switzerland, 8063
    • Stadtspital Waid ; Triemli, Site Triemli - clinic for Medical oncology & hematology
• Taiwan
  • Kaohsiung City, Taiwan, 00824
    • E-DA hospital
  • Niaosong, Taiwan, 00833
    • Chang Gung Memorial Hospital Cgmh - Kaohsiung Branch
  • Taichung, Taiwan, 40705
    • Taichung Veterans General Hospital
  • Taichung, Taiwan, 00420
    • Chung Shan Medical University Hospital
  • Tainan, Taiwan, 00704
    • National Cheng Kung University Hospital NCKUH
  • Tainan, Taiwan, 00736
    • Chi Mei Medical Center CMMC - Liouying Branch
  • Taipei, Taiwan, 00100
    • National Taiwan University Hospital NTUH
  • Taoyuan, Taiwan, 333
    • Linkou Chang Gung Memorial Hospital
• United Kingdom
  • London, United Kingdom, NW1 2BU
    • University College Hospital
  • Manchester, United Kingdom, M20 4BX
    • The Christie Hospital
  • Middlesbrough, United Kingdom, TS4 3BW
    • The James Cook University Hospital
• United States
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Ironwood Cancer and Research Center
  • California
    • Anaheim, California, United States, 92835
      • St. Joseph Heritage Healthcare
    • Glendale, California, United States, 91204
      • The Oncology Institute of Hope and Innovation
    • La Jolla, California, United States, 92093
      • University of California San Diego
    • Los Angeles, California, United States, 90095
      • UCLA
    • Whittier, California, United States, 90602
      • PIH Health
  • Florida
    • Hollywood, Florida, United States, 33021
      • Memorial Healthcare System- Memorial Cancer Institute
    • Orlando, Florida, United States, 32806
      • Orlando Health
    • Tallahassee, Florida, United States, 32308
      • Florida Cancer Specialists
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60637
      • University of Chicago
  • Indiana
    • Fort Wayne, Indiana, United States, 46804
      • Ft. Wayne Medical Oncology and Hematology
  • Kentucky
    • Louisville, Kentucky, United States, 40207
      • Baptist Health Louisville
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Baton Rouge General
  • Maryland
    • Bethesda, Maryland, United States, 20817
      • American Oncology Partners of Maryland
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber Cancer Institute
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • OptumCare Cancer Care
  • New Jersey
    • Manahawkin, New Jersey, United States, 08050
      • Meridian Hematology and Oncology
    • Somerset, New Jersey, United States, 08873
      • Astera Cancer Care
  • New York
    • Bronx, New York, United States, 10461
      • Montefiore Medical Center
  • North Carolina
    • Asheville, North Carolina, United States, 28806
      • Messino Cancer Centers
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center
  • Rhode Island
    • Providence, Rhode Island, United States, 02908
      • Roger Williams Medical Center
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105
      • Avera Cancer Institute
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute
  • Texas
    • Fort Worth, Texas, United States, 76104
      • The Center for Cancer and Blood Disorders
  • Utah
    • Salt Lake City, Utah, United States, 84106
      • Utah Cancer Specialists
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia Health System
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialist
  • Washington
    • Kennewick, Washington, United States, 99336
      • Kadlec Clinic Hematology and Oncology
    • Tacoma, Washington, United States, 98405
      • Northwest Medical Specialties

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Participants eligible for inclusion in the study must meet all inclusion criteria within 28 days of randomization into the study.

• Sign and date the inform consent form (ICF) prior to the start of any study specific qualification procedures.
• Adults ≥18 years (if the legal age of consent is >18 years old, then follow local regulatory requirements)
• Life expectancy ≥3 months
• Has pathologically documented Stage IIIB, IIIC, or stage IV NSCLC disease with or without actionable genomic alterations (AGA) at the time of randomization (based on the American Joint Committee on Cancer, Eighth Edition) and meets following criteria for NSCLC:

• Participants without AGA:

  1. Must have documented negative test results for epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK).
  2. Must have no known genomic alterations in ROS proto-oncogene 1 (ROS1), neurotrophic tyrosine receptor kinase (NTRK), proto oncogene B-raf (BRAF), mesenchymal-epithelial transition (MET) exon 14 skipping, or rearranged during transfection (RET).
• Participants with AGA must have one or more documented actionable genomic alteration(s): EGFR, ALK, ROS1, NTRK, BRAF, MET exon 14 skipping, or RET.
• Has documentation of radiographic disease progression while on or after receiving the most recent treatment regimen for advanced or metastatic NSCLC.

• Participant without AGA must meet 1 of the following prior therapy requirements for advanced or metastatic NSCLC:

  1. Received platinum-based chemotherapy in combination with α-PD-1/α-PD-L1 monoclonal antibody as the only prior line of therapy.

     • Includes participants who received prior platinum-based/chemotherapy with or without radiotherapy with maintenance α-PD-1/α-PD-L1 monoclonal antibody for Stage III disease and relapsed/progressed within 6 months from the last dose of platinum-based chemotherapy.
     • Includes participants who received prior platinum-based/chemotherapy with or without radiotherapy (with or without maintenance α-PD-1/α-PD-L1 monoclonal antibody) for Stage III disease and subsequently received α-PD-1/α-PD-L1 monoclonal antibody therapy (with or without platinum-based chemotherapy) for recurrent disease.
  2. Received platinum-based chemotherapy and α-PD-1/α-PD-L1 monoclonal antibody (in either order) sequentially as the only 2 prior lines of therapy.

• Participants with AGA must meet the following for advanced or metastatic NSCLC:

  1. Participants who have been treated with 1 or 2 prior lines of applicable targeted therapy that is locally approved for the participant's genomic alteration at the time of screening;

     • Participants who have tumors with EGFR L858R or exon 19 deletion mutations must have received prior Osimertinib.
     • Those who received a targeted agent as adjuvant therapy for early-stage disease must have relapsed or progressed while on the treatment or within 6 months of the last dose OR received at least one additional course of targeted therapy for the same genomic alteration (which may or may not be same agent used in the adjuvant setting) for relapsed/progressive disease.
     • Participants who have been treated with a prior TKI must receive additional approved targeted therapy, if locally available and clinically appropriate, for the applicable genomic alteration, or the participant will not be allowed in the study.

  2. Participants who have received platinum-based chemotherapy as the only prior line of cytotoxic therapy:

     • One platinum-containing regimen for advanced disease
     • Those who received a platinum-containing regimen as adjuvant therapy for early-stage disease must have relapsed or progressed while on the treatment or within 6 months of the last dose OR received at least one additional course of platinum-containing therapy (which may or may not be same as in the adjuvant setting) for relapsed/progressive disease.
  3. May have received up to one α-PD-1/α-PD-L1 monoclonal antibody alone or in combination with a cytotoxic agent.
• Must undergo a pre-treatment tumor biopsy procedure or if available, tumor tissue previously retrieved from a biopsy procedure performed within 2 years prior to the participant signing informed consent and that has a minimum of 10 × 4 micron sections or a tissue block equivalent of 10 × 4 micron sections may be substituted for the pre-treatment biopsy procedure during Screening. If a documented law or regulation prohibits (or does not approve) sample collection, then such samples will not be collected/submitted
• Measurable disease based on local imaging assessment using RECIST v1.1
• Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1 at Screening
• Within 7 days before randomization, has adequate bone marrow, hepatic, and renal function
• Left ventricular ejection fraction (LVEF) ≥50% by either echocardiogram (ECHO) or multigated acquisition (MUGA) scan within 28 days before randomization
• Adequate blood clotting function defined as international normalized ratio/prothrombin time and either partial thromboplastin or activated partial thromboplastin time ≤1.5 × upper limit of normal (ULN)
• Adequate treatment washout period before randomization
• Females of childbearing potential must have a negative serum pregnancy test at screening and must be willing to use highly effective birth control from the time of enrollment up to 7 months after the last dose of DS-1062a or for at least 6 months after the last dose of docetaxel
• Males must be surgically sterile or must use a condom in addition to highly effective birth control if his partners are of reproductive potential from the time of enrollment and for at least 4 months after last dose of DS-1062a or for at least 6 months after the last dose of docetaxel
• Male participants must not freeze or donate sperm from the time of Screening and throughout the study period and for at least 4 months after the last dose of DS-1062a or for at least 6 months after the last dose of docetaxel
• Female participants must not donate, or retrieve for their own use, ova from the time of Screening and throughout the study period and for at least 7 months after the last dose of DS-1062a and for at least 6 months after the last dose of docetaxel

Exclusion Criteria:

• Mixed small-cell lung cancer (SCLC) and NSCLC histology
• Has spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. Participants with clinically inactive brain metastases may be included in the study. Participants with treated brain metastases who are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy.
• Has leptomeningeal carcinomatosis or metastasis

• Had prior treatment with:

  • Any agent including antibody drug conjugate (ADC) containing a chemotherapeutic agent targeting topoisomerase I
  • TROP2-targeted therapy
  • Docetaxel
• Had prior treatment with platinum-based chemotherapy and prior immunotherapy for Stage II NSCLC disease (eg, in the neo-adjuvant or adjuvant setting) without subsequently meeting the prior therapy requirements for Stage III or metastatic NSCLC disease
• Has NSCLC disease that is eligible for definitive local therapy alone

• Has uncontrolled or significant cardiac disease, including:

  • Mean QT interval corrected for heart rate using Fridericia's formula >470 msec (based on the average of Screening triplicate 12-lead electrocardiogram [ECG] determinations).
  • Myocardial infarction or uncontrolled/unstable angina within 6 months before randomization
  • Congestive heart failure (CHF) (New York Heart Association Class II to IV) at Screening. Participants with a history of Class II to IV CHF prior to Screening, must have returned to Class I CHF and have LVEF ≥50% (by either an ECHO or MUGA scan within 28 days before randomization) in order to be eligible.
  • Uncontrolled or significant cardiac arrhythmia
  • LVEF <50% by ECHO or MUGA scan within 28 days before randomization
  • Uncontrolled hypertension (resting systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg) within 28 days before randomization
• Has a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at Screening
• Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (ie, pulmonary emboli within 3 months before randomization, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, pleural effusion, etc.), or any autoimmune, connective tissue or inflammatory disorders with pulmonary involvement (ie, rheumatoid arthritis, Sjogren's syndrome, sarcoidosis, etc.), or prior pneumonectomy.
• Significant third-space fluid retention (for example ascites or pleural effusion) and is not amenable for required repeated drainage
• Clinically significant corneal disease
• Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals; suspected infections (eg, prodromal symptoms); or inability to rule out infections
• Has known human immunodeficiency virus (HIV) infection that is not well controlled
• Has an active or uncontrolled hepatitis B and/or hepatitis C infection, is positive for hepatitis B or C virus based on the evaluation of results of tests for hepatitis B (hepatitis B surface antigen [HBsAg], anti-hepatitis B surface antibody [anti-HBs], anti-hepatitis B core antibody [anti-HBc], or hepatitis B virus [HBV] DNA), and/or hepatitis C infection (as per hepatitis C virus [HCV] RNA) within 28 days of randomization.
• Has a history of malignancy, other than NSCLC, except adequately resected non-melanoma skin cancer, curatively treated in situ disease, or other solid tumors curatively treated, with no evidence of disease for ≥3 years
• Toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet improved to NCI-CTCAE version 5.0 Grade ≤1 or baseline
• Has a history of severe hypersensitivity reactions to either the drug substances, inactive ingredients (including but not limited to polysorbate 80) of DS-1062a or docetaxel, or monoclonal antibodies
• Pregnant or breastfeeding
• Has substance abuse or any other medical conditions such as clinically significant cardiac or psychological conditions

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DS-1062a 6.0 mg/kg; Participants will be randomized to receive 6.0 mg/kg of DS-1062a.	Drug: DS-1062a; DS-1062a will be administered as an intravenous (IV) infusion on Day 1 of each 3-week cycle; Other Names: Datopotamab deruxtecan (Dato-DXd)
Active Comparator: Docetaxel 75 mg/m^2; Participants will be randomized to receive 75 mg/m^2 docetaxel.	Drug: Docetaxel; Docetaxel will be administered as an IV infusion on Day 1 of each 3-week cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS) As Assessed by Blinded Independent Central Review (BICR) Per RECIST v1.1 Following DS-1062a Versus Docetaxel	PFS is defined as the time from randomization to the earlier of the dates of the first documentation of radiographic progressive disease or death due to any cause.	From randomization until disease progression or death (whichever occurs first), up to approximately 43 months
Overall Survival (OS) Following DS-1062a Versus Docetaxel	OS is defined as the time from randomization to the date of death due to any cause.	From randomization until date of death due to any cause, up to approximately 43 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS) As Assessed by Investigator Per RECIST v1.1 Following DS-1062a Versus Docetaxel	PFS is defined as the time from randomization to the earlier of the dates of the first documentation of radiographic progressive disease or death due to any cause.	From randomization until disease progression or death (whichever occurs first), up to approximately 43 months
Objective Response Rate (ORR) As Assessed by Blinded Independent Central Review (BICR) and Investigator As Per RECIST v1.1 Following DS-1062a Versus Docetaxel	ORR is defined as the proportion of participants with a best overall response of complete response (CR) or partial response (PR).	From randomization until disease progression or death (whichever occurs first), up to approximately 43 months
Duration of Response (DOR) As Assessed by Blinded Independent Central Review (BICR) and Investigator As Per RECIST v1.1 Following DS-1062a Versus Docetaxel	DOR is defined as the time from the date of the first documentation of objective response (confirmed CR or confirmed PR) to the date of the first documentation of radiographic PD or death due to any cause, whichever occurs first.	From date of first objective response (CR or PR) to date of first radiographic disease progression or death due to any cause (whichever occurs first), up to approximately 43 months
Disease Control Rate (DCR) As Assessed by Blinded Independent Central Review (BICR) and Investigator As Per RECIST v1.1 Following DS-1062a Versus Docetaxel	DCR is defined as the proportion of participants who achieved a best overall response (BOR) of CR, PR, or stable disease (SD).	From randomization until disease progression or death (whichever occurs first), up to approximately 43 months
Time to Response (TTR) As Assessed by Blinded Independent Central Review (BICR) and Investigator As Per RECIST v1.1 Following DS-1062a Versus Docetaxel	TTR is defined as the time from randomization to the date of the first documentation of objective response (CR or PR) in responding participants.	From randomization to date of first objective response (CR or PR), up to approximately 43 months
Time to Deterioration (TTD) Following DS-1062a Versus Docetaxel	TTD is defined as the time from randomization to the first onset of a ≥10-point increase in cough, chest pain, or dyspnea, confirmed by a second ≥10-point increase from randomization in the same symptom at the next scheduled assessment, or confirmed by death within 21 days of the first ≥10-point increase from randomization.	Baseline and assessed on Day 15 of each cycle until disease progression or end of treatment (each cycle is 21 days) and then once more at +90 days end of treatment
Percentage of Participants Who Reported Treatment-emergent Adverse Events Following DS-1062a Versus Docetaxel	Reported treatment-emergent adverse events, serious adverse events, adverse events of special interest, and those considered related to the study drug or study procedures, or that are associated with study treatment reduction, interruption, or discontinuation.	Baseline up to 35 days after last study dose, up to approximately 43 months
Pharmacokinetic Parameter Maximum Plasma Concentration (Cmax) of DS-1062a, Total Anti-Trophoblast cell surface protein 2 (Anti-TROP2) Antibody, and Active Metabolite MAAA-1181a		Cycle 1, Day 1: predose and 30 minutes, 3 hours, 5 hours, and 7 hours postdose and Days 2, 4, 8, and 15; Cycles 2, 3, 4, 6, and 8, Day 1: predose and 1 hour postdose (each cycle is 21 days)
Pharmacokinetic Parameter Time to Maximum Plasma Concentration (Tmax) of DS-1062a, Total Anti-TROP2 Antibody, and Active Metabolite MAAA-1181a		Cycle 1, Day 1: predose and 30 minutes, 3 hours, 5 hours, and 7 hours postdose and Days 2, 4, 8, and 15; Cycles 2, 3, 4, 6, and 8, Day 1: predose and 1 hour postdose (each cycle is 21 days)
Pharmacokinetic Parameter Area Under the Plasma Concentration-Time Curve (AUC) of DS-1062a, Total Anti-TROP2 Antibody, and Active Metabolite MAAA-1181a	Area under the plasma concentration-time curve up to last quantifiable time (AUClast) and area under the plasma concentration-time curve during dosing interval (AUCtau) will be assessed.	Cycle 1, Day 1: predose and 30 minutes, 3 hours, 5 hours, and 7 hours postdose and Days 2, 4, 8, and 15; Cycles 2, 3, 4, 6, and 8, Day 1: predose and 1 hour postdose (each cycle is 21 days)
Proportion of Participants Who Are Anti-Drug Antibody (ADA)-Positive (Baseline and Post-Baseline) and Proportion of Participants Who Have Treatment-emergent ADA		Cycle 1, Day 1 predose; Cycle 1, Day 8; Cycles 2, 4, and subsequent cycles, Day 1 predose; end of treatment; 28-day safety follow up; and long-term survival follow up every 3 months, up to approximately 43 months (each cycle is 21 days)

Collaborators and Investigators

• Sponsor: Daiichi Sankyo
• Collaborators: AstraZeneca
• Investigators: Study Director: Global Clinical Leader, Daiichi Sankyo

Study record dates

Study Major Dates

• Study Start (Actual): December 21, 2020
• Primary Completion (Estimated): May 10, 2024
• Study Completion (Estimated): June 27, 2024

Study Registration Dates

• First Submitted: November 19, 2020
• First Submitted That Met QC Criteria: November 30, 2020
• First Posted (Actual): December 7, 2020

Study Record Updates

• Last Update Posted (Actual): April 10, 2024
• Last Update Submitted That Met QC Criteria: April 9, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Docetaxel; Non-small Cell Lung Cancer; Advanced Non-small Cell Lung Cancer; Metastatic Non-small Cell Lung Cancer; DS-1062; Datopotamab Deruxtecan (Dato-DXd)
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Docetaxel
• Other Study ID Numbers: DS1062-A-U301; 2020-004643-80 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
• IPD Sharing Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• IPD Sharing Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No