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)

Non-small Cell Lung Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04656652
• Other study ID #: DS1062-A-U301
• Secondary ID: 2020-004643-80
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: December 21, 2020
• Est. completion date: June 27, 2024

Study information

• Verified date: May 2024
• Source: Daiichi Sankyo
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 590
• Est. completion date: June 27, 2024
• Est. primary completion date: May 10, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 a-PD-1/a-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 a-PD-1/a-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 a-PD-1/a-PD-L1 monoclonal antibody) for Stage III disease and subsequently received a-PD-1/a-PD-L1 monoclonal antibody therapy (with or without platinum-based chemotherapy) for recurrent disease.

2. Received platinum-based chemotherapy and a-PD-1/a-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 a-PD-1/a-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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small Cell Lung Cancer

Intervention

Drug:
• DS-1062a
DS-1062a will be administered as an intravenous (IV) infusion on Day 1 of each 3-week cycle
• Docetaxel
Docetaxel will be administered as an IV infusion on Day 1 of each 3-week cycle.

Locations

Country	Name	City	State
Argentina	CER San Juan	Buenos Aires
Argentina	Centro de Investigacion Pergamino S.A.	Pergamino
Argentina	Gaston Martinengo	Rosario
Argentina	Instituto de OncologÃÂ-a de Rosario	Rosario
Australia	Flinders Medical Centre	Bedford Park
Australia	Blacktown Hosital	Blacktown
Australia	Austin Hospital	Heidelberg
Australia	Macquarie Hospital	North Ryde
Australia	Crown Princess Mary Cancer Centre Westmead Hospital	Sydney
Australia	Southern Medical Day Care Centre	Wollongong
Belgium	Centre Hospitalier Jolimont-Lobbes	Haine-Saint-Paul
Belgium	CHA Centre Hospitalier de l Ardenne	Libramont
Belgium	CHR site de la Citadelle	Liège
Belgium	CHU UCL Namur	Yvoir
Brazil	Instituto do Cancer do Ceara - ICC	Fortaleza
Brazil	Hospital Nossa Senhora da Conceição	Porto Alegre
Brazil	Hospital Sao Lucas da Pucrs	Porto Alegre
Brazil	Instituto Nacional de Cancer-INCA	Rio De Janeiro
Brazil	Hospital de Base de Sao Jose do Rio Preto	São José Do Rio Preto
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	MUHC-Glen Site and MUHC Research Institute	Montréal	Quebec
Canada	Sunnbrook Health Sciences Centre	Toronto	Ontario
Canada	University Health Network - Princess Margaret Hospital	Toronto	Ontario
China	Beijing Cancer Hospital	Beijing
China	Linyi Cancer Hospital	Hangzhou
China	The First Affiliated Hospital of Zhejiang University	Hangzou
China	Harbin Medical University Cancer Hospital	Heilongjiang
China	Jiamusi Cancer Tuberculosis Hospital	Heilongjiang
China	Fudan University Shanghai Cancer Center	Henan
China	Hubei Cancer Hospital	Hubei
China	The First Affiliated Hospital of Xi'an Jiaotong University	Shandong
China	Shanghai Chest Hospital	Shanghai
China	Henan Cancer Hospital	Shanghai Sheng
China	Zhejiang Cancer Hospital	Shanxi
China	West China Hospital, Sichuan University	Sichuan Province
China	Tianjin Medical University Cancer Institute and Hospital	Tianjin
China	Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology	Wuhan
China	Sir Run Run Shaw Hospital Zhejiang University School of Medicine	Zhejiang
Czechia	Vseobecna Fakultni Nemocnice VFN	Praha
France	Hopital Jean Minjoz	Besançon
France	Centre Hospitalier Universitaire de Grenoble	Grenoble
France	Centre Leon Berard	Lyon
France	CHU Louis Pradel	Lyon
France	APHM - Hopital Nord	Marseille
France	University Hospital of Nantes - Thoracic Oncology	Nantes
France	Institut Curie	Paris
France	CHU de Poitier Pole regional de Cancerologie	Poitiers
France	Hopital Pontchaillou	Rennes
France	Hopitaux Universitaire de Strasbourg	Strasbourg
France	Hopital Foch	Sureesnes
France	CHU Toulouse Hopital Larrey	Toulouse
France	Gustav Roussy Cancer Campus Grand Paris	Villejuif
Germany	Charite - Universitaetsmedizin Berlin	Berlin
Germany	Evangelische Lungenklinik Berlin	Berlin
Germany	IKF Krankenhaus Nordwest	Frankfurt am main
Germany	Universitaetsklinikum Freiburg	Freiburg
Germany	Asklepios Fachklinik Muenchen-Gauting	Gauting
Germany	Thoraxklinik Heidelberg gGmbH	Heidelberg
Germany	Lungenklinik Hemer	Hemer
Germany	Klinikverbund Allgäu	Kempten
Germany	Universitaet zu Koeln - Uniklinik Koeln	Koeln
Germany	Medizinische Klinik V	Standort Gießen
Germany	Klinikum Traunstein	Traunstein
Hong Kong	Prince of Wales Hospital / The Chinese University of Hong Kong	Hong Kong
Hong Kong	Queen Mary Hospital	Hong Kong
Hungary	Orszagos Koranyi TBC es Pulmonologiai Intezet	Budapest
Hungary	Uzsoki Utcai Korhaz	Budapest
Hungary	Szent Borbala Korhaz	Tatabánya
Hungary	Tolna Megyei Balassa Janos Korhaz	Tolna
Hungary	Tudogyogyintezet Torokbalint	Torokbalint
Italy	Azienda Ospedaliero- Universitaria Policlinico S. Orsola-Malpighi	Bologna
Italy	Azienda Ospedaliera Universitaria Policlinico G Rodolico San Marco	Catania
Italy	ASL 3 Genovese Oncologia Medica Villa Scassi	Genova
Italy	Fondazione IRCCS Istituto Nazionale Tumori	Milan
Italy	Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico	Milano
Italy	IRCCS Istituto Europeo di Oncologia	Milano
Italy	Azienda Ospedaliero-Universitaria San Luigi Gonzaga	Orbassano
Italy	Fondazione Policlinico Universitario Agostino Gemelli IRCCS	Roma
Italy	Instituicao de Fisioterapeutas Ocupacionais	Roma
Japan	Hyogo Cancer Center	Akashi
Japan	Niigata Cancer Center Hospital	Chuo Ku
Japan	Kyushu University Hospital	Fukuoka
Japan	Saitama Medical University International Medical Center	Hidaka
Japan	Kansai Medical University Hospital	Hirakata
Japan	Kanazawa University Hospital	Kanazawa
Japan	National Cancer Center Hospital East	Kashiwa
Japan	The Cancer Institute Hospital of JFCR	Koto-Ku
Japan	Kyoto University Hospital	Kyoto
Japan	NHO Shikoku Cancer Center	Matsuyama
Japan	Shizuoka Cancer Center	Nagaizumi-cho
Japan	Okayama University Hospital	Okayama
Japan	Osaka International Cancer Institute	Osaka
Japan	Kindai University Hospital	Osaka-sayama
Japan	Osaka City General Hospital	Osaka-shi
Japan	Saitama Cancer Center	Saitama
Japan	Sendai Kousei Hospital	Sendai-shi
Japan	NHO Hokkaido Cancer Center	Shiroishi
Japan	Tokushima University Hospital	Tokushima
Japan	National Cancer Center Hospital	Tokyo
Japan	Fujita Health University Hospital	Toyoake
Korea, Republic of	Chungbuk National University Hospital	Cheongju-si
Korea, Republic of	Kyungpook National University Chilgok Hospital	Daegu
Korea, Republic of	St. Vincents Hospital The Catholic University of Korea	Gyeonggi-do
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Kangbuk Samsung Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Boramae Medical Center	Seoul
Korea, Republic of	The Catholic University of Korea, Seoul St. Marys Hospital	Seoul
Korea, Republic of	Yonsei University Health System - Severance Hospital	Seoul
Mexico	San Peregrino Cancer Center	Aguascalientes
Mexico	Hospital Medica Sur Tlalpan	Ciudad de mexico
Mexico	Hospital Civil de Guadalajara Fray Antonio Alcalde	Guadalajara
Mexico	Hospital Universitario Jose Eleuterio Gonzalez	Monterrey
Netherlands	Erasmus MC	Amsterdam
Netherlands	Amphia Ziekenhuis	Breda
Netherlands	Isala Klinieken	Harderwijk
Netherlands	St. Jansdal Ziekenhuis	Rotterdam
Poland	II Klinika Chorob Pluc i Gruzlicy	Bialystok
Poland	Szpitale Pomorskie Sp.zo.o	Gdynia
Poland	Ms Pneumed	Lublin
Poland	SP Zespol Gruzlicy i Chorob Pluc	Olsztyn
Poland	Med Polonia Sp. z o.o.	Poznan
Poland	Szpital Specjalistyczny w Prabutach Sp. z o.o.	Prabuty
Poland	Oddzial Onkologii Wojewódzki Szpital Specjalistyczny Slupsk	Slupsk
Poland	Magodent Sp. z.o.o Szpital Elblaska	Warsaw
Poland	Maria Sklodowska-Curie National Research Institute of Oncology	Warsaw
Puerto Rico	FDI Clinical Research	San Juan
Romania	SC Oncopremium Team SRL	Baia Mare
Romania	Centrul Medical Sanador	Bucharest
Romania	Institutul Oncologic Profesor Doctor Alexandru Trestioreanu	Bucuresti
Romania	Clinical Emergency Hospital	Constanta
Romania	Onco Clinic Consult SA	Craiova
Romania	Oncolab SRL	Craiova
Romania	Sf Nectarie Oncology Center	Craiova
Romania	SC Oncomed SRL	Timisoara
Russian Federation	Kursk Regional Clinical Oncology Dispensary	Kursk
Russian Federation	Federal State Budgetary Institution - N.N. Blokhin National Medical Research Center of Oncology	Moscow
Russian Federation	Institute of Oncology Hadassah Moscow	Moscow
Russian Federation	University Headache Clinic LLC	Moscow
Russian Federation	VitaMed LLC	Moscow
Russian Federation	LLC MSCH "Klinitsist"	Novosibirsk
Russian Federation	N.N. Petrov Research Institute of Oncology	Saint Petersburg
Singapore	ICON Cancer Centre Farrer Park Hospital	Singapore
Singapore	National Cancer Centre Singapore	Singapore
Singapore	OncoCare Cancer Centre - Gleneagles Medical Centre Location	Singapore
Spain	Hospital Clinic i Provincial de Barcelona	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital Universitario Vall d'Hebron	Barcelona
Spain	Hospital Puerte de Hierro de Majadahonda	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario Fundacion Jimenez Diaz	Madrid
Spain	Hospital Regional Universitario Málaga	Málaga
Spain	CHUO	Ourense
Spain	Hospital Universitario de Valme	Sevilla
Spain	Hospital Virgen Macarena	Sevilla
Spain	Hospital General Universitario de Valencia	Valencia
Spain	Hospital Universitari i Politecnic La Fe	Valencia
Spain	Hospital Clinico Universitario Lozano Bleza	Zaragoza
Switzerland	Inselspital Universitätsspital Bern	Bern
Switzerland	Kantonsspital St. Gallen	Saint Gallen
Switzerland	Stadtspital Waid ; Triemli, Site Triemli - clinic for Medical oncology & hematology	Zürich
Taiwan	E-Da Hospital	Kaohsiung City
Taiwan	Chang Gung Memorial Hospital CGMH - Kaohsiung Branch	Niaosong
Taiwan	Chung Shan Medical University Hospital	Taichung
Taiwan	Taichung Veterans General Hospital	Taichung
Taiwan	Chi Mei Medical Center CMMC - Liouying Branch	Tainan
Taiwan	National Cheng Kung University Hospital NCKUH	Tainan
Taiwan	National Taiwan University Hospital NTUH	Taipei
Taiwan	LinKou Chang Gung Memorial Hospital	Taoyuan
United Kingdom	University College Hospital	London
United Kingdom	The Christie Hospital	Manchester
United Kingdom	The James Cook University Hospital	Middlesbrough
United States	St. Joseph Heritage Healthcare	Anaheim	California
United States	Messino Cancer Centers	Asheville	North Carolina
United States	Baton Rouge General	Baton Rouge	Louisiana
United States	American Oncology Partners of Maryland	Bethesda	Maryland
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Montefiore Medical Center	Bronx	New York
United States	Ironwood Cancer and Research Center	Chandler	Arizona
United States	University of Virginia Health System	Charlottesville	Virginia
United States	Northwestern University	Chicago	Illinois
United States	University of Chicago	Chicago	Illinois
United States	University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	Virginia Cancer Specialist	Fairfax	Virginia
United States	Ft. Wayne Medical Oncology and Hematology	Fort Wayne	Indiana
United States	The Center for Cancer and Blood Disorders	Fort Worth	Texas
United States	The Oncology Institute of Hope and Innovation	Glendale	California
United States	Memorial Healthcare System- Memorial Cancer Institute	Hollywood	Florida
United States	Kadlec Clinic Hematology and Oncology	Kennewick	Washington
United States	University of California San Diego	La Jolla	California
United States	OptumCare Cancer Care	Las Vegas	Nevada
United States	UCLA	Los Angeles	California
United States	Baptist Health Louisville	Louisville	Kentucky
United States	Meridian Hematology and Oncology	Manahawkin	New Jersey
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Orlando Health	Orlando	Florida
United States	Roger Williams Medical Center	Providence	Rhode Island
United States	Utah Cancer Specialists	Salt Lake City	Utah
United States	Avera Cancer Institute	Sioux Falls	South Dakota
United States	Astera Cancer Care	Somerset	New Jersey
United States	Northwest Medical Specialties	Tacoma	Washington
United States	Florida Cancer Specialists	Tallahassee	Florida
United States	PIH Health	Whittier	California

Sponsors (2)

Lead Sponsor	Collaborator
Daiichi Sankyo	AstraZeneca

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Canada,  China,  Czechia,  France,  Germany,  Hong Kong,  Hungary,  Italy,  Japan,  Korea, Republic of,  Mexico,  Netherlands,  Poland,  Puerto Rico,  Romania,  Russian Federation,  Singapore,  Spain,  Switzerland,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)