Study of DS-1062a in Advanced or Metastatic Non-small Cell Lung Cancer With Actionable Genomic Alterations (TROPION-Lung05)

Phase 2, Single-arm, Open-label Study of DS-1062a in Advanced or Metastatic Non-small Cell Lung Cancer With Actionable Genomic Alterations and Progressed On or After Applicable Targeted Therapy and Platinum Based Chemotherapy (TROPION-Lung05)

This is a study of the efficacy, pharmacokinetics, and safety of DS-1062a in participants with advanced or metastatic non-small cell lung cancer (NSCLC) with known actionable genomic alterations.

Study Overview

• Status: Completed
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: DS-1062a

Detailed Description

This study will evaluate DS-1062a 6.0 mg/kg in participants with advanced or metastatic NSCLC with actionable genomic alterations and who have been previously been treated with 1 platinum-containing therapy and 1 or more lines of targeted therapy. The study will be divided into 3 periods: Screening Period, Treatment Period, and Follow-up Period. The primary analysis of Objective Response Rate (ORR) by blinded Independent Central Review (BICR) will be conducted after all participants either have been followed for at least 9 months after the start of study treatment or have discontinued from the study, whichever occurs first.

• Study Type: Interventional
• Enrollment (Actual): 137
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Lyon, France, 69003
    • CHU Louis Pradel
  • Paris, France, 75005
    • Institut Curie
  • Strasbourg, France, 67091
    • Hopitaux Universitaire de Strasbourg- Nouvel Hopital Civil
  • Toulon, France, 83000
    • Centre Hospitalier Intercommunal Toulon La Seyne sur mer Hopital Sainte-Musse
  • Bouches-Du-Rhône
    • Marseille, Bouches-Du-Rhône, France, 13015
      • APHM - Hopital Nord
  • Loire-Atlantique
    • Nantes, Loire-Atlantique, France, 44000
      • University Hospital of Nantes
  • Occitanie
    • Toulouse, Occitanie, France, 31059
      • CHU Toulouse Hopital Larrey
  • Rhone
    • Lyon, Rhone, France, 69008
      • Centre Léon Bérard
  • Île-de-France Region
    • Villejuif, Île-de-France Region, France, 94805
      • Gustav Roussy Cancer Campus Grand Paris
• Germany
  • Hanover, Germany, 30625
    • Medizinische Hochschule Hannover
  • Heidelberg, Germany, 69126
    • Thoraxklinik Heidelberg gGmbH
  • Baden-Wurttemberg
    • Heidelberg, Baden-Wurttemberg, Germany, 69126
      • Thoraxklinik Heidelberg
  • Bavaria
    • Gauting, Bavaria, Germany, 82131
      • Asklepios Fachklinik Muenchen-Gauting
  • Hesse
    • Frankfurt am Main, Hesse, Germany, 60488
      • IKF Krankenhaus Nordwest
  • North Rhine-Westphal
    • Cologne, North Rhine-Westphal, Germany, 50937
      • Universitaet zu Koeln - Uniklinik Koeln
• Hungary
  • Budapest, Hungary, H-1121
    • National Koranyi Institute for TB and Pulmonology
  • Törökbálint, Hungary, H-2045
    • Pulmonology Hospital Torokbalint
• Italy
  • Bologna, Italy, 40138
    • Azienda Ospedaliero-Universitaria S. Orsola Malpighi
  • Milan, Italy, 20141
    • Istituto Europeo di Oncologia
  • Milan, Italy, 20122
    • Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
  • Parma, Italy, 43126
    • Azienda Ospedaliero Universitaria di Parma
  • Reggio Emilia, Italy, 42123
    • Azienda Ospedaliera Arcispedale Santa Maria
  • CT
    • Catania, CT, Italy, 95030
      • Azienda Ospedaliera Universitaria Policlinico-OVE
  • RM
    • Rome, RM, Italy, 00168
      • Fondazione Policlinico Universitario Agostino Gemelli IRCCS
  • Torino
    • Orbassano, Torino, Italy, 10043
      • University of Turin San Luigi Hospital
• Japan
  • Aichi, Japan, 464-8681
    • Aichi Cancer Center Hospital
  • Aichi-ken
    • Toyoake-shi, Aichi-ken, Japan, 470-1192
      • Fujita Health University Hospital
  • Chiba
    • Kashiwa-shi, Chiba, Japan, 277-8577
      • National Cancer Center Hospital East
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 003-0804
      • Hokkaido Cancer Center
  • Kyoto
    • Kyoto, Kyoto, Japan, 606-8507
      • Kyoto University Hospital
  • Niigata
    • Niigata, Niigata, Japan, 961-8566
      • Niigata Cancer Center Hospital
  • Osaka
    • Hirakata-shi, Osaka, Japan, 573-1191
      • Kansai Medical University Hospital
    • Osaka, Osaka, Japan, 541-8567
      • Osaka International Cancer Institute
    • Osaka, Osaka, Japan, 534-0021
      • Osaka City General Hospital
    • Ōsaka-sayama, Osaka, Japan, 589-8511
      • Kindai University Hospital
  • Shizuoka
    • Nagaizumi-chō, Shizuoka, Japan, 411-8777
      • Shizuoka Cancer Center
  • Tokushima
    • Tokushima, Tokushima, Japan, 770-8503
      • Tokushima University Hospital
  • Tokyo
    • Chuo Ku, Tokyo, Japan, 104-0045
      • National Cancer Center Hospital
    • Koto-Ku, Tokyo, Japan, 135-8550
      • The Cancer Institute Hospital of Jfcr
• Netherlands
  • North Holland
    • Amsterdam, North Holland, Netherlands, 1066 CX
      • The Netherlands Cancer Institute
  • South Holland
    • Rotterdam, South Holland, Netherlands, 3015 CD
      • Erasmus MC
• South Korea
  • Seoul, South Korea, 03080
    • Seoul National University Hospital
  • Seoul, South Korea, 05505
    • Asan Medical Center
  • Seoul, South Korea, 03722
    • Severance Hospital
  • Seoul, South Korea, 6273
    • Samsung Medical Center
  • Gyeonggi-do
    • Seongnam-si, Gyeonggi-do, South Korea, 110744
      • Seoul National University Bundang Hospital
• Spain
  • Alicante, Spain, 03010
    • Hospital General Universitario de Alicante
  • Barcelona, Spain, 08036
    • Hospital Clinic i Provincial de Barcelona
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall dHebron
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Madrid
    • Majadahonda, Madrid, Spain, 28222
      • Hospital Universitario Puerta de Hierro de Majadahonda
  • Malaga
    • Málaga, Malaga, Spain, 29010
      • Hospital Regional Universitario Malaga
• Taiwan
  • Tainan, Taiwan, 70403
    • National Cheng Kung University Hospital
  • Taipei, Taiwan, 11217
    • Taipei Veterans General Hospital
  • Taipei, Taiwan, 112
    • Koo Foundation Sun Yat-Sen Cancer Center
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital NTUH
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85259
      • Mayo Clinic
  • California
    • La Jolla, California, United States, 92093
      • University of California San Diego
    • Santa Monica, California, United States, 90404
      • UCLA
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Boca Raton Regional Hospital
    • Gainesville, Florida, United States, 32605
      • Sarah Cannon Research Institute at Florida Cancer Center, North
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic
    • Orlando, Florida, United States, 32804
      • AdventHealth Orlando
    • Port Charlotte, Florida, United States, 33980
      • Sarah Cannon Research Institute at Florida Cancer Center, South
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • Maryland
    • Chevy Chase, Maryland, United States, 20815
      • The Office of Dr. Frederick P. Smith MD
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital Cancer Center
  • Michigan
    • Detroit, Michigan, United States, 48202
      • University of Michigan
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New Jersey
    • East Brunswick, New Jersey, United States, 08816
      • XCancer / Regional Cancer Care Associate (Astera)
  • New York
    • New York, New York, United States, 10065
      • Weill Cornell Medical College
    • New York, New York, United States, 10016
      • NYU Langone Medical Center
    • Port Jefferson, New York, United States, 11776
      • New York Cancer and Blood Specialists
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Case Medical Center
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105
      • Avera Cancer Institute Sioux Falls
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Sarah Cannon Research Institute at Tennessee Oncology - Chattanooga
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute
  • Texas
    • Dallas, Texas, United States, 75230
      • Mary Crowley Cancer Research
    • Houston, Texas, United States, 77030
      • University of Texas MD Anderson Cancer Center
  • Virginia
    • Athens, Virginia, United States, 30607
      • Virginia Cancer Specialists
  • Washington
    • Kennewick, Washington, United States, 99336
      • Kadlec Clinic Hematology and Oncology
    • Seattle, Washington, United States, 33612
      • Seattle Cancer Care Alliance

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 for this 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)

• Has pathologically documented NSCLC that:

  1. Has stage IIIB, IIIC, or stage IV NSCLC disease at the time of enrollment (based on the American Joint Committee on Cancer, Eighth Edition).
  2. Has one or more of the following documented activating genomic alterations: EGFR, ALK, ROS1, NTRK, BRAF, MET exon 14 skipping, or RET.

KRAS mutations in the absence of any of the genomic alterations specified above will be excluded.

Overexpression of EGFR, in the absence of activating mutations, is NOT sufficient for enrollment.

Participants who have not received osimertinib should be evaluated for the presence of EGFR T790M mutation after relapse/progression on/after the most recent EGFR tyrosine kinase inhibitor (TKI), unless the participant is already known to be positive with document results for this mutation or unless osimertinib is not locally approved.

• Has documentation of radiographic disease progression while on or after receiving the most recent treatment regimen for advanced or metastatic NSCLC.

• Participant must meet the following for advanced or metastatic NSCLC:

  1. Has been treated with at least one but no more than two cytotoxic agent-containing therapy in the metastatic setting:

     • One platinum-containing regimen (either as monotherapy or combination therapy).
     • May have received up to one additional line of cytotoxic agent-containing therapy.
     • 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.
  2. May have received up to one checkpoint inhibitor (CPI)-containing regimen (may be in combination with a cytotoxic agent as part of a regimen described above or as an additional CPI regimen without a cytotoxic agent).

  3. Has been treated with 1 or more lines of non-CPI targeted therapy that is locally approved for the participant's applicable genomic alteration at the time of screening:

     • Those who received a targeted agent for the applicable genomic alterations in the study 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 alterations (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 targeted therapy, if clinically appropriate, for the genomic alterations that are considered amenable or the participant will not be allowed in the study.
• Must undergo a mandatory pre-treatment tumor biopsy procedure or if available, a tumor biopsy that was recently collected (within 3 months of screening) after completion of the most recent anticancer treatment regimen 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 mandatory biopsy collected during screening.
• Measurable disease based on local imaging assessment using RECIST v1.1.
• Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 - 1 at screening.

Exclusion Criteria:

Participants meeting any exclusion criteria for this study will be excluded from this study.

• 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.
• Has leptomeningeal carcinomatosis.

• Has prior treatment with:

  1. Any chemotherapeutic agent targeting topoisomerase I, including antibody drug conjugate (ADC) containing such agent.
  2. TROP2-targeted therapy.

• Uncontrolled or significant cardiovascular disease:

  1. History of myocardial infarction within 6 months prior to Cycle 1 Day 1.
  2. History of uncontrolled angina pectoris within 6 months prior to Cycle 1 Day 1.
  3. Symptomatic 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 of Cycle 1 Day 1) in order to be eligible.
  4. History of serious cardiac arrhythmia requiring treatment.
  5. LVEF <50% or institutional lower limit of normal by ECHO or MUGA scan.
  6. Uncontrolled hypertension (resting systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg).
• 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
• Clinically significant corneal disease.
• Has other primary malignancies, 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DS-1062a 6.0 mg/kg; Participants will receive 6.0 mg/kg of DS-1062a	Drug: DS-1062a; DS-1062a will be administered as an intravenous (IV) infusion once every 3 weeks; Other Names: Datopotamab Deruxtecan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Objective Response Rate (ORR) Based on Blinded Independent Central Review (BICR)	ORR is defined as the proportion of participants with a best overall response of confirmed complete response (CR) or confirmed partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.	From baseline until disease progression, death, or other protocol defined reason, up to approximately 24 months.

Secondary Outcome Measures

Outcome Measure	Time Frame
Duration of Response (DOR)	From baseline up to approximately 24 months
Progression-free Survival (PFS)	From baseline up to approximately 24 months
Overall Survival (OS)	From baseline up to approximately 24 months
Pharmacokinetic Parameter Maximum Concentration (Cmax)	From baseline up to approximately 24 months
Pharmacokinetic Parameter Time to Maximum Concentration (Tmax)	From baseline up to approximately 24 months
Pharmacokinetic Parameter Area Under the Concentration-Time Curve (AUC)	From baseline up to approximately 24 months
Percentage of Participants Who Reported Treatment-emergent Adverse Events (TEAE)	From baseline up to approximately 24 months

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Sands J, Ahn MJ, Lisberg A, Cho BC, Blumenschein G Jr, Shum E, Pons Tostivint E, Goto Y, Yoh K, Heist R, Shimizu J, Lee JS, Baas P, Planchard D, Perol M, Felip E, Su WC, Zebger-Gong H, Lan L, Liu C, Howarth P, Chiaverelli R, Paz-Ares L. Datopotamab Deruxtecan in Advanced or Metastatic Non-Small Cell Lung Cancer With Actionable Genomic Alterations: Results From the Phase II TROPION-Lung05 Study. J Clin Oncol. 2025 Apr;43(10):1254-1265. doi: 10.1200/JCO-24-01349. Epub 2025 Jan 6.

Study record dates

Study Major Dates

• Study Start (Actual): March 30, 2021
• Primary Completion (Actual): March 10, 2023
• Study Completion (Actual): February 4, 2026

Study Registration Dates

• First Submitted: July 20, 2020
• First Submitted That Met QC Criteria: July 20, 2020
• First Posted (Actual): July 23, 2020

Study Record Updates

• Last Update Posted (Actual): March 24, 2026
• Last Update Submitted That Met QC Criteria: March 20, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Non-small Cell Lung Cancer; Datopotamab Deruxtecan; DS-1062a; Metastatic Non-small Cell Lung Cancer; Advanced Metastatic Non-small Cell Lung Cancer
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: DS1062-A-U202; 2020-002774-27 (EudraCT Number); 2024-511449-21-00 (Ctis)

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