A Study to Investigate the Efficacy and Safety of Dato-DXd With or Without Osimertinib Compared With Platinum Based Doublet Chemotherapy in Participants With EGFR-Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer
TROPION-Lung15
A Phase III, Open-label, Sponsor-blind, Randomized Study of Dato-DXd With or Without Osimertinib Versus Platinum-based Doublet Chemotherapy for Participants With EGFR-mutated Locally Advanced or Metastatic Non-small Cell Lung Cancer Whose Disease Has Progressed on Prior Osimertinib Treatment (TROPION-Lung15)
2 other identifiers
interventional
744
27 countries
302
Brief Summary
This study will assess the effect of Dato-DXd in combination with osimertinib or Dato-DXd monotherapy versus platinum-based doublet chemotherapy in terms of progression-free survival (PFS).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Oct 2024
Typical duration for phase_3
302 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 13, 2024
CompletedFirst Posted
Study publicly available on registry
May 16, 2024
CompletedStudy Start
First participant enrolled
October 4, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 30, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
September 27, 2028
March 2, 2026
February 1, 2026
2 years
May 13, 2024
February 27, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Progression free Survival (PFS)
PFS is defined as the time from randomization to Blinded Independent Central Review (BICR)-assessed progression using RECIST v1.1 or death due to any cause, regardless of whether the participant withdraws from study therapy, receives other anti-cancer therapy, or clinical progression.
Up to 2.5 years
Secondary Outcomes (12)
Overall Survival (OS)
Up to 3.5 years
Central Nervous System Progression-free Survival (CNS PFS)
Up to 2.5 years
Objective Response Rate (ORR)
Up to 2.5 years
Duration of Response (DoR)
Up to 2.5 years
Progression-free Survival-2 (PFS-2)
Up to 3.5 years
- +7 more secondary outcomes
Study Arms (3)
Group 1: Dato-DXd + Osimertinib Combination Therapy
EXPERIMENTALParticipants will receive Dato-DXd 6 milligrams per kilogram (mg/kg) as intravenous (IV) infusion every 3 weeks (Q3W) on Day 1 of every 21-day cycle, and osimertinib 80 milligrams (mg) once daily (QD) orally, until RECIST v1.1-defined radiological progression by investigator, unacceptable toxicity, or other discontinuation criterion is met.
Group 2: Dato-DXd Monotherapy
EXPERIMENTALParticipants will receive Dato-DXd 6 mg/kg as IV infusion Q3W on Day 1 of every 21-day cycle, until RECIST v1.1-defined radiological progression by investigator, unacceptable toxicity, or other discontinuation criterion is met.
Group 3: Platinum-based Doublet Chemotherapy
EXPERIMENTALParticipants will receive pemetrexed 500 milligrams per meter square (mg/m2) in combination with carboplatin (AUC5) or cisplatin 75 mg/m2 as IV infusion Q3W for 4 cycles followed by pemetrexed maintenance 500 mg/m2 as IV infusion Q3W, until RECIST v1.1-defined radiological progression by investigator, unacceptable toxicity, or another discontinuation criterion is met.
Interventions
Dato-DXd will be administered as IV infusion.
Osimertinib will be administered orally.
Pemetrexed will be administered as IV infusion.
Carboplatin will be administered as IV infusion.
Cisplatin will be administered as IV infusion.
Eligibility Criteria
You may qualify if:
- Histologically or cytologically confirmed non-squamous NSCLC.
- Must have evidence of documented pre-existing EGFRm information (EGFRm known to be associated with (epidermal growth factor receptor \[EGFR\] tyrosine kinase inhibitor \[TKis\] sensitivity \[Ex19del, L858R, G719X, S768I, or L861Q\], either alone or in combination with other EGFR mutations, which may include T790M).
- Documented extra-cranial radiologic progression on prior osimertinib monotherapy (as most recent line of treatment) in the adjuvant, locally advanced, or metastatic setting.
- Less than or equal to (\<=2) prior lines of EGFR TKIs (osimertinib is the only permitted prior third generation EGFR TKI).
- At least one lesion, not previously irradiated, that qualifies as a RECIST v1.1 TL at baseline and can be accurately measured at baseline.
- World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Adequate bone marrow reserve and organ function within 7 days before randomization.
You may not qualify if:
- Use of chemotherapy, vascular endothelial growth factor inhibitor, immunotherapy or any anti-cancer therapy in the metastatic setting. Platinum-based chemotherapy in non-metastatic setting within 12 months prior to randomization.
- History of another primary malignancy except for malignancy treated with curative intent with no known active disease within 2 years before the first dose of study intervention.
- Any evidence of severe or uncontrolled systemic diseases, including, but not limited to active bleeding diseases, active infection, active ILD/pneumonitis, cardiac disease.
- Has significant third-space fluid retention (example \[eg.\], ascites or pleural effusion) as judged by the investigator and is not amenable for required repeated drainage.
- History of non-infectious ILD/pneumonitis including radiation pneumonitis that required steroids or drug-induced ILD, has current ILD/pneumonitis, or has suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.
- Has severe pulmonary function compromise resulting from intercurrent pulmonary illnesses.
- Unstable spinal cord compression and/or unstable brain metastases.
- Participants with symptomatic brain metastases (including leptomeningeal involvement).
- Clinically significant corneal disease.
- Uncontrolled infection requiring systemic antibiotics, antivirals, or antifungals, suspected infections or inability to rule out infections. Use of systemic antibiotics within 14 days of randomization.
- Has known human immunodeficiency virus (HIV) infection that is not well controlled.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AstraZenecalead
- Daiichi Sankyocollaborator
Study Sites (302)
Research Site
Fayetteville, Arkansas, 72703, United States
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Duarte, California, 91010, United States
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Fountain Valley, California, 92708, United States
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La Jolla, California, 92093, United States
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Los Angeles, California, 90048, United States
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San Diego, California, 92123, United States
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Colorado Springs, Colorado, 80909, United States
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Fort Collins, Colorado, 80528, United States
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Gainesville, Florida, 32608, United States
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Jacksonville, Florida, 32256, United States
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Athens, Georgia, 30607, United States
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Chicago, Illinois, 60611, United States
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Evanston, Illinois, 60201, United States
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Louisville, Kentucky, 40207, United States
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Baltimore, Maryland, 21201, United States
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Bethesda, Maryland, 20817, United States
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Boston, Massachusetts, 02114, United States
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Boston, Massachusetts, 02215, United States
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Boston, Massachusetts, 02215, United States
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Detroit, Michigan, 48202, United States
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Kansas City, Missouri, 64132, United States
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Omaha, Nebraska, 68124, United States
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Morristown, New Jersey, 07960, United States
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Northfield, New Jersey, 08225, United States
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New York, New York, 10016, United States
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New York, New York, 10065, United States
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The Bronx, New York, 10461, United States
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Maumee, Ohio, 43537, United States
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Philadelphia, Pennsylvania, 19107, United States
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Pittsburgh, Pennsylvania, 15232, United States
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Chattanooga, Tennessee, 37404, United States
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Nashville, Tennessee, 37203, United States
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Fairfax, Virginia, 22031, United States
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Seattle, Washington, 98104, United States
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Fitzroy, VIC3065, Australia
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Heidelberg, 3084, Australia
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Kogarah, 2217, Australia
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Liverpool, 2170, Australia
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Nedlands, 6009, Australia
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Port Macquarie, 2444, Australia
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St Leonards, 2065, Australia
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Westmead, 2145, Australia
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Woodville, 5011, Australia
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Woolloongabba, 4102, Australia
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Charleroi, 6060, Belgium
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Edegem, 2650, Belgium
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Ghent, 9000, Belgium
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Hasselt, 3500, Belgium
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Jette, 1090, Belgium
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La Louvière, 7100, Belgium
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Leuven, 3000, Belgium
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Namur, 5000, Belgium
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Roeselare, 8800, Belgium
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Barretos, 14784-400, Brazil
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Betim, 32671-550, Brazil
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Blumenau, 89010-340, Brazil
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Florianópolis, 88040-970, Brazil
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Itajaí, 88301-220, Brazil
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Pelotas, 96020-080, Brazil
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Porto Alegre, 90035-074, Brazil
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Porto Alegre, 90470-340, Brazil
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Porto Alegre, 90610-000, Brazil
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Rio de Janeiro, 22250-905, Brazil
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Rio de Janeiro, 22281-100, Brazil
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Rio de Janeiro, 22775-001, Brazil
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São Paulo, 01323-900, Brazil
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São Paulo, 01327-001, Brazil
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Brampton, Ontario, L6R 3J7, Canada
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Newmarket, Ontario, L3Y 2P9, Canada
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Toronto, Ontario, M4N 3M5, Canada
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Toronto, Ontario, M5G 1Z5, Canada
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Montreal, Quebec, H4A 3J1, Canada
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Québec, Quebec, G1R 2J6, Canada
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Baoding, 071000, China
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Beijing, 100005, China
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Beijing, 100034, China
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Beijing, 100044, China
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Beijing, 100050, China
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Beijing, 100142, China
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Beijing, 100730, China
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Beijing, 101199, China
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Bengbu, 233004, China
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Changchun, 130012, China
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Changchun, 130021, China
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Changsha, 410013, China
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Chengdu, 610041, China
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Deyang, 618000, China
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Ganzhou, 341099, China
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Guangzhou, 510180, China
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Hangzhou, 310003, China
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Hangzhou, 310022, China
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Hefei, 230001, China
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Hengyang, 421001, China
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Huaian, 223399, China
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Jinan, 250013, China
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Linyi, 276000, China
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Luoyang, 471003, China
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Luzhou, 646000, China
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Nanchang, 330006, China
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Nanjing, 210009, China
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Shanghai, 200433, China
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Shantou, China
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Shenyang, 110004, China
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Shenyang, 110042, China
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Tianjin, 300201, China
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Tianjin, CN-300052, China
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Weifang, 261000, China
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Wuhan, 430060, China
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Zhengzhou, 450000, China
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Zhengzhou, 450001, China
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Zhengzhou, 450008, China
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Angers, 49933, France
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Avignon, 84902, France
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Bordeaux, 33076, France
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Caen, 14000, France
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Lille, 59037, France
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Montpellier, 34298, France
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Nantes, 44093, France
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Paris, 75014, France
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Paris, 75970, France
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Pessac, 33604, France
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Quimper, 29000, France
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Toulon Armees, 83800, France
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Toulouse, 31400, France
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Tours, 37000, France
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Villejuif, 94805, France
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Berlin, 12351, Germany
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Berlin-Zehlendorf, 14165, Germany
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Bonn, 53127, Germany
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Essen, 45122, Germany
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Georgsmarienhütte, 49124, Germany
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Giessen, 35392, Germany
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Großhansdorf, 22927, Germany
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Hamburg, 20251, Germany
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Hamburg, 21075, Germany
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Heidelberg, 69126, Germany
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Kempten, 87439, Germany
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Löwenstein, 74245, Germany
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Nuremberg, 90419, Germany
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Oldenburg, 26121, Germany
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Athens, 11526, Greece
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Athens, 11527, Greece
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Athens, 12462, Greece
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Athens, 18547, Greece
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Heraklion, 71110, Greece
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Thessaloniki, 552 36, Greece
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Thessaloniki, 56249, Greece
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Thessaloniki, 57001, Greece
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Thessaloniki, 57010, Greece
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Hong Kong, 999077, Hong Kong
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Hong Kong, 999077, Hong Kong
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Hong Kong, Hong Kong
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Hong Kong, Hong Kong
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Shatin, 00000, Hong Kong
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Amravati, 444606, India
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Bhubaneswar, 751019, India
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Hyderabad, 500034, India
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Kolhāpur, 416234, India
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Mumbai, 400012, India
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Mysuru, 570017, India
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Namakkal, 637001, India
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Pune, 411001, India
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Raipur, 492001, India
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Rajasthan, 313001, India
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Ranchi, 834001, India
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Thane, 401107, India
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Trivandrum, 695011, India
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Varanasi, 221005, India
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Beersheba, 8410101, Israel
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Haifa, 3109601, Israel
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Haifa, 34362, Israel
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Jerusalem, 91031, Israel
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Jerusalem, 91120, Israel
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Kfar Saba, 4428164, Israel
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Petah Tikva, 49100, Israel
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Ramat Gan, 52621, Israel
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Tel Aviv, 62748, Israel
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Bari, 70124, Italy
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Milan, 20141, Italy
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Misterbianco, 95045, Italy
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Monza, 20090, Italy
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Naples, 80131, Italy
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Orbassano, 10043, Italy
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Padua, 35128, Italy
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Parma, 43126, Italy
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Perugia, 06100, Italy
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Roma, 00144, Italy
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Rozzano, 20089, Italy
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Verona, 37126, Italy
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Bunkyō City, 113-8431, Japan
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Bunkyō City, 113-8603, Japan
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Fukuoka, 812-8582, Japan
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Hiroshima, 734-8551, Japan
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Iruma-Gun, 350-0495, Japan
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Iwakuni-shi, 740-8510, Japan
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Kobe, 650-0046, Japan
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Kōtoku, 135-8550, Japan
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Kumamoto, 860-8556, Japan
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Kyoto, 602-8566, Japan
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Matsuyama, 791-0280, Japan
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Nagoya, 464-8681, Japan
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Nagoya, 466-8560, Japan
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Niigata, 951-8566, Japan
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Osaka, 534-0021, Japan
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Osaka, 541-8567, Japan
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Ōsaka-sayama, 589-8511, Japan
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Sendai, 981-0914, Japan
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Sunto-gun, 411-8777, Japan
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Toyoake-shi, 470-1192, Japan
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Utsunomiya, 320-0834, Japan
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Wakayama, 641-8510, Japan
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Yokohama, 236-0051, Japan
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Yokohama, 241-8515, Japan
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Alor Star, 05460, Malaysia
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Cheras, 56000, Malaysia
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Johor Bahru, 81100, Malaysia
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Kuala Lumpur, 59100, Malaysia
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Kuala Selangor, 46050, Malaysia
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Kuching, 93586, Malaysia
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Perai, 13700, Malaysia
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Petaling Jaya, 47500, Malaysia
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Amersfoort, 3813 TZ, Netherlands
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Harderwijk, 3844 DG, Netherlands
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Rotterdam, 3015 GD, Netherlands
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Zutphen, 7207 AE, Netherlands
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Bacolod, 6100, Philippines
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Cebu City, 6000, Philippines
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Davao City, 8000, Philippines
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Manila, 1000, Philippines
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Quezon, 1102, Philippines
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Quezon, 1104, Philippines
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San Juan City, 1500, Philippines
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Katowice, 40-519, Poland
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Krakow, 30-727, Poland
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Lodz, 90-302, Poland
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Olsztyn, 10-357, Poland
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Poznan, 60-569, Poland
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Braga, 4710, Portugal
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Lisbon, 1500-650, Portugal
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Loures, 2674-514, Portugal
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Porto, 4099-001, Portugal
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Porto, 4200-072, Portugal
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Craiova, 200385, Romania
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Craiova, 200542, Romania
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Singapore, 168583, Singapore
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Singapore, 217562, Singapore
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Singapore, 308433, Singapore
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Busan, 48108, South Korea
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Chungcheongbuk-do, 28644, South Korea
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Goyang-si, 10408, South Korea
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Gyeonggi-do, 13620, South Korea
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Jinju, 52727, South Korea
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Seoul, 03080, South Korea
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Seoul, 03722, South Korea
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Seoul, 06351, South Korea
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Seoul, 06591, South Korea
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Seoul, 5505, South Korea
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Suwon, 16247, South Korea
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A Coruña, 15009, Spain
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Barakaldo, 48903, Spain
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Barcelona, 08003, Spain
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Barcelona, 08041, Spain
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El Palmar, 30120, Spain
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L'Hospitalet de Llobregat, 08908, Spain
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Madrid, 28027, Spain
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Madrid, 28046, Spain
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Majadahonda, 28222, Spain
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Málaga, 29004, Spain
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Oviedo, 33006, Spain
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Palma de Mallorca, 7120, Spain
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Pamplona, 31008, Spain
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Santander, 39008, Spain
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Santiago de Compostela-Coruña, 15706, Spain
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Seville, 41014, Spain
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Valencia, 46010, Spain
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Valencia, 46026, Spain
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Valladolid, 47003, Spain
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Changhua, 50006, Taiwan
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Kaohsiung City, 80756, Taiwan
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New Taipei City, 23561, Taiwan
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Taichung, 404, Taiwan
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Taichung, 40705, Taiwan
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Tainan, 70403, Taiwan
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Tainan, 73657, Taiwan
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Taipei, 100, Taiwan
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Taipei, 110, Taiwan
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Taipei, 112, Taiwan
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Bangkok, 10330, Thailand
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Bangkok, 10400, Thailand
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Bangkok, 10700, Thailand
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Chiang Mai, 50200, Thailand
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Hat Yai, 90110, Thailand
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Khon Kaen, 40002, Thailand
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Pathum Thani, 12120, Thailand
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Birmingham, B9 5SS, United Kingdom
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Cambridge, CB2 0QQ, United Kingdom
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Glasgow, G12 0YN, United Kingdom
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Leicester, LE1 5WW, United Kingdom
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London, EC1A 7BE, United Kingdom
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Manchester, M20 4BX, United Kingdom
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Middlesbrough, TS4 3BW, United Kingdom
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Hanoi, 100000, Vietnam
Related Publications (1)
Tan DS, Nadal E, Cheema P, Wu YL, Ahn MJ, Tanizaki J, Grainger E, Nizialek E, Forcina A, van der Gronde T, Yu HA. TROPION-Lung15: a randomized phase III study of osimertinib combined with datopotamab deruxtecan (Dato-DXd) or Dato-DXd alone versus platinum-doublet chemotherapy in patients with EGFR-mutated advanced non-small cell lung cancer and whose disease has progressed on prior osimertinib. Ther Adv Med Oncol. 2025 Dec 23;17:17588359251385410. doi: 10.1177/17588359251385410. eCollection 2025.
PMID: 41466843DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Central Study Contacts
AstraZeneca Clinical Study Information Center
CONTACT
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 13, 2024
First Posted
May 16, 2024
Study Start
October 4, 2024
Primary Completion (Estimated)
September 30, 2026
Study Completion (Estimated)
September 27, 2028
Last Updated
March 2, 2026
Record last verified: 2026-02
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- Time Frame
- AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
- Access Criteria
- When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. "Yes", indicates that AZ are accepting requests for IPD, but this does not mean all requests will be approved.