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

NCT ID: NCT04484142

Last Updated: 2025-11-10

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 137 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-03-30
• Study Completion Date: 2025-12-12

Brief Summary

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.

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.

Conditions

Non-small Cell Lung Cancer

Keywords

Metastatic Non-small Cell Lung Cancer; Advanced Metastatic Non-small Cell Lung Cancer; Non-small Cell Lung Cancer; DS-1062a; Datopotamab Deruxtecan

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

DS-1062a 6.0 mg/kg

Participants will receive 6.0 mg/kg of DS-1062a

Group Type: EXPERIMENTAL

DS-1062a

Intervention Type: DRUG

DS-1062a will be administered as an intravenous (IV) infusion once every 3 weeks

Interventions

DS-1062a

DS-1062a will be administered as an intravenous (IV) infusion once every 3 weeks

Intervention Type: DRUG

Other Intervention Names

Datopotamab Deruxtecan

Eligibility Criteria

Inclusion Criteria

• 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

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AstraZeneca

INDUSTRY

Sponsor Role: collaborator

Daiichi Sankyo

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Global Clinical Leader

Role: STUDY_DIRECTOR

Daiichi Sankyo

Locations

Mayo Clinic

Phoenix, Arizona, United States

University of California San Diego

La Jolla, California, United States

UCLA

Santa Monica, California, United States

Boca Raton Regional Hospital

Boca Raton, Florida, United States

Sarah Cannon Research Institute at Florida Cancer Center, North

Gainesville, Florida, United States

Mayo Clinic

Jacksonville, Florida, United States

AdventHealth Orlando

Orlando, Florida, United States

Sarah Cannon Research Institute at Florida Cancer Center, South

Port Charlotte, Florida, United States

Moffitt Cancer Center

Tampa, Florida, United States

The Office of Dr. Frederick P. Smith MD

Chevy Chase, Maryland, United States

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

University of Michigan

Detroit, Michigan, United States

Mayo Clinic

Rochester, Minnesota, United States

Washington University School of Medicine

St Louis, Missouri, United States

XCancer / Regional Cancer Care Associate (Astera)

East Brunswick, New Jersey, United States

NYU Langone Medical Center

New York, New York, United States

Weill Cornell Medical College

New York, New York, United States

New York Cancer and Blood Specialists

Port Jefferson, New York, United States

University Hospitals Case Medical Center

Cleveland, Ohio, United States

Avera Cancer Institute Sioux Falls

Sioux Falls, South Dakota, United States

Sarah Cannon Research Institute at Tennessee Oncology - Chattanooga

Chattanooga, Tennessee, United States

Sarah Cannon Research Institute

Nashville, Tennessee, United States

Mary Crowley Cancer Research

Dallas, Texas, United States

University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Virginia Cancer Specialists

Athens, Virginia, United States

Kadlec Clinic Hematology and Oncology

Kennewick, Washington, United States

Seattle Cancer Care Alliance

Seattle, Washington, United States

APHM - Hopital Nord

Marseille, Bouches-Du-Rhône, France

University Hospital of Nantes

Nantes, Loire-Atlantique, France

CHU Toulouse Hopital Larrey

Toulouse, Occitanie, France

Centre Leon Berard

Lyon, Rhone, France

CHU Louis Pradel

Lyon, , France

Institut Curie

Paris, , France

Hopitaux Universitaire de Strasbourg- Nouvel Hopital Civil

Strasbourg, , France

Centre Hospitalier Intercommunal Toulon La Seyne sur mer Hopital Sainte-Musse

Toulon, , France

Gustav Roussy Cancer Campus Grand Paris

Villejuif, Île-de-France Region, France

Thoraxklinik Heidelberg

Heidelberg, Baden-Wurttemberg, Germany

Asklepios Fachklinik Muenchen-Gauting

Gauting, Bavaria, Germany

IKF Krankenhaus Nordwest

Frankfurt am Main, Hesse, Germany

Universitaet zu Koeln - Uniklinik Koeln

Cologne, North Rhine-Westphal, Germany

Medizinische Hochschule Hannover

Hanover, , Germany

Thoraxklinik Heidelberg gGmbH

Heidelberg, , Germany

National Koranyi Institute for TB and Pulmonology

Budapest, , Hungary

Pulmonology Hospital Törökbálint

Törökbálint, , Hungary

Azienda Ospedaliera Universitaria Policlinico-OVE

Catania, CT, Italy

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Rome, RM, Italy

University of Turin San Luigi Hospital

Orbassano, Torino, Italy

Azienda Ospedaliero-Universitaria S. Orsola Malpighi

Bologna, , Italy

Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico

Milan, , Italy

Istituto Europeo di Oncologia

Milan, , Italy

Azienda Ospedaliero Universitaria di Parma

Parma, , Italy

Azienda Ospedaliera Arcispedale Santa Maria

Reggio Emilia, , Italy

Fujita Health University Hospital

Toyoake-shi, Aichi-ken, Japan

National Cancer Center Hospital East

Kashiwa-shi, Chiba, Japan

Hokkaido Cancer Center

Sapporo, Hokkaido, Japan

Kyoto University Hospital

Kyoto, Kyoto, Japan

Niigata Cancer Center Hospital

Niigata, Niigata, Japan

Kansai Medical University Hospital

Hirakata-shi, Osaka, Japan

Osaka City General Hospital

Osaka, Osaka, Japan

Osaka International Cancer Institute

Osaka, Osaka, Japan

Kindai University Hospital

Ōsaka-sayama, Osaka, Japan

Shizuoka Cancer Center

Nagaizumi-chō, Shizuoka, Japan

Tokushima University Hospital

Tokushima, Tokushima, Japan

National Cancer Center Hospital

Chuo Ku, Tokyo, Japan

The Cancer Institute Hospital of JFCR

Koto-Ku, Tokyo, Japan

Aichi Cancer Center Hospital

Aichi, , Japan

The Netherlands Cancer Institute

Amsterdam, North Holland, Netherlands

Erasmus MC

Rotterdam, South Holland, Netherlands

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, South Korea

Seoul National University Hospital

Seoul, , South Korea

Severance Hospital

Seoul, , South Korea

Asan Medical Center

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

Hospital Universitario Puerta de Hierro de Majadahonda

Majadahonda, Madrid, Spain

Hospital Regional Universitario Malaga

Málaga, Malaga, Spain

Hospital General Universitario de Alicante

Alicante, , Spain

Hospital Universitario Vall dHebron

Barcelona, , Spain

Hospital Clinic i Provincial de Barcelona

Barcelona, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

National Cheng Kung University Hospital

Tainan, , Taiwan

National Taiwan University Hospital NTUH

Taipei, , Taiwan

Taipei Veterans General Hospital

Taipei, , Taiwan

Koo Foundation Sun Yat-Sen Cancer Center

Taipei, , Taiwan

Countries

United States; France; Germany; Hungary; Italy; Japan; Netherlands; South Korea; Spain; Taiwan

References

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.

Reference Type: DERIVED

PMID: 39761483 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2020-002774-27

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

DS1062-A-U202

Identifier Type: -

Identifier Source: org_study_id