Metastatic Non-small Cell Lung CancerPhase 3TROPION-Lung15NCT06417814
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
A Phase 3 study testing Dato-DXd, Osimertinib and Pemetrexed in people with Metastatic Non-small Cell Lung Cancer, run by AstraZeneca at 211 sites in 24 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 130 years
- Conditions the study is for
- Metastatic Non-small Cell Lung Cancer
- What is being tested?
- Dato-DXd, Osimertinib and Pemetrexed
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 768 participants
- Where
- 211 sitesin 24 countries
- Study dates
- 4 Oct 2024to 27 Sep 2028
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 130 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- - 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.
Who cannot join
- - 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.
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- -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.
Trial locations and contacts
211 sites in 24 countries.
211 sites in 24 countries
China34 sites
Research Site
Baoding, 071000
Research Site
Beijing, 100005
Research Site
Beijing, 100034
Research Site
Beijing, 100050
Research Site
Beijing, 100142
Research Site
Beijing, 100730
Research Site
Beijing, 101199
Research Site
Bengbu, 233004
Research Site
Changchun, 130021
Research Site
Changsha, 410013
Research Site
Chengdu, 610041
Research Site
Deyang, 618000
Research Site
Ganzhou, 341099
Research Site
Guangzhou, 510180
Research Site
Hangzhou, 310003
Research Site
Hangzhou, 310022
Research Site
Hefei, 230001
Research Site
Hengyang, 421001
Research Site
Jinan, 250013
Research Site
Linyi, 276000
Research Site
Luoyang, 471003
Research Site
Luzhou, 646000
Research Site
Nanchang, 330006
Research Site
Nanjing, 210009
Research Site
Shanghai, 200433
Research Site
Shantou
Research Site
Shenyang, 110004
Research Site
Shenyang, 110042
Research Site
Tianjin, CN-300052
Research Site
Weifang, 261000
Research Site
Wuhan, 430060
Research Site
Zhengzhou, 450000
Research Site
Zhengzhou, 450001
Research Site
Zhengzhou, 450008
Japan22 sites
Research Site
Bunkyō City, 113-8431
Research Site
Bunkyō City, 113-8603
Research Site
Fukuoka, 812-8582
Research Site
Hiroshima, 734-8551
Research Site
Iruma-Gun, 350-0495
Research Site
Iwakuni-shi, 740-8510
Research Site
Kobe, 650-0046
Research Site
Kōtoku, 135-8550
Research Site
Kumamoto, 860-8556
Research Site
Kyoto, 602-8566
Research Site
Matsuyama, 791-0280
Research Site
Nagoya, 466-8560
Research Site
Niigata, 951-8566
Research Site
Osaka, 534-0021
Research Site
Osaka, 541-8567
Research Site
Ōsaka-sayama, 589-8511
Research Site
Sendai, 981-0914
Research Site
Sunto-gun, 411-8777
Research Site
Toyoake-shi, 470-1192
Research Site
Utsunomiya, 320-0834
Research Site
Wakayama, 641-8510
Research Site
Yokohama, 241-8515
Spain16 sites
Research Site
A Coruña, 15009
Research Site
Barakaldo, 48903
Research Site
Barcelona, 08003
Research Site
Barcelona, 08041
Research Site
El Palmar, 30120
Research Site
L'Hospitalet de Llobregat, 08908
Research Site
Madrid, 28046
Research Site
Majadahonda, 28222
Research Site
Málaga, 29004
Research Site
Palma de Mallorca, 7120
Research Site
Pamplona, 31008
Research Site
Santiago de Compostela-Coruña, 15706
Research Site
Seville, 41014
Research Site
Valencia, 46010
Research Site
Valencia, 46026
Research Site
Valladolid, 47003
Italy11 sites
Research Site
Bari, 70124
Research Site
Milan, 20141
Research Site
Misterbianco, 95045
Research Site
Monza, 20090
Research Site
Naples, 80131
Research Site
Orbassano, 10043
Research Site
Padova, 35128
Research Site
Perugia, 06100
Research Site
Roma, 00144
Research Site
Rozzano, 20089
Research Site
Verona, 37126
France10 sites
Research Site
Bordeaux, 33076
Research Site
Caen, 14000
Research Site
Lille, 59037
Research Site
Montpellier, 34298
Research Site
Nantes, 44093
Research Site
Paris, 75014
Research Site
Pessac, 33604
Research Site
Toulon Armees, 83800
Research Site
Toulouse, 31400
Research Site
Villejuif, 94805
South Korea10 sites
Research Site
Busan, 48108
Research Site
Chungcheongbuk-do, 28644
Research Site
Goyang-si, 10408
Research Site
Gyeonggi-do, 13620
Research Site
Seoul, 03080
Research Site
Seoul, 03722
Research Site
Seoul, 06351
Research Site
Seoul, 06591
Research Site
Seoul, 5505
Research Site
Suwon, 16247
Taiwan10 sites
Research Site
Changhua, 50006
Research Site
Kaohsiung City, 80756
Research Site
New Taipei City, 23561
Research Site
Taichung, 404
Research Site
Taichung, 407219
Research Site
Tainan, 70403
Research Site
Tainan, 73657
Research Site
Taipei, 100
Research Site
Taipei, 110
Research Site
Taipei, 112
United States9 sites
Research Site
Fayetteville, Arkansas, 72703
Research Site
Fountain Valley, California, 92708
Research Site
Jacksonville, Florida, 32256
Research Site
Kansas City, Missouri, 64132
Research Site
Maumee, Ohio, 43537
Research Site
Nashville, Tennessee, 37203
Research Site
New York, New York, 10065
Research Site
Pittsburgh, Pennsylvania, 15232
Research Site
San Diego, California, 92123
Australia8 sites
Research Site
Fitzroy, VIC3065
Research Site
Heidelberg, 3084
Research Site
Kogarah, 2217
Research Site
Liverpool, 2170
Research Site
Nedlands, 6009
Research Site
St Leonards, 2065
Research Site
Westmead, 2145
Research Site
Woolloongabba, 4102
Brazil8 sites
Research Site
Barretos, 14784-400
Research Site
Betim, 32671-550
Research Site
Porto Alegre, 90470-340
Research Site
Porto Alegre, 90610-000
Research Site
Rio de Janeiro, 22250-905
Research Site
Rio de Janeiro, 22281-100
Research Site
Rio de Janeiro, 22775-001
Research Site
São Paulo, 01327-001
Germany8 sites
Research Site
Berlin-Zehlendorf, 14165
Research Site
Essen, 45122
Research Site
Georgsmarienhütte, 49124
Research Site
Großhansdorf, 22927
Research Site
Hamburg, 20251
Research Site
Hamburg, 21075
Research Site
Löwenstein, 74245
Research Site
Nuremberg, 90419
India8 sites
Research Site
Hyderabad, 500034
Research Site
Kolhāpur, 416234
Research Site
Mumbai, 400012
Research Site
Namakkal, 637001
Research Site
Pune, 411001
Research Site
Ranchi, 834001
Research Site
Thane, 401107
Research Site
Varanasi, 221005
Belgium7 sites
Research Site
Charleroi, 6060
Research Site
Edegem, 2650
Research Site
Ghent, 9000
Research Site
Hasselt, 3500
Research Site
Jette, 1090
Research Site
Namur, 5000
Research Site
Roeselare, 8800
Israel7 sites
Research Site
Haifa, 3109601
Research Site
Haifa, 34362
Research Site
Jerusalem, 91031
Research Site
Kfar Saba, 4428164
Research Site
Petah Tikva, 49100
Research Site
Ramat Gan, 52621
Research Site
Tel Aviv, 62748
Malaysia7 sites
Research Site
Alor Star, 05460
Research Site
Johor Bahru, 81100
Research Site
Kuala Lumpur, 59100
Research Site
Kuala Selangor, 46050
Research Site
Kuching, 93586
Research Site
Perai, 13700
Research Site
Petaling Jaya, 47500
United Kingdom6 sites
Research Site
Birmingham, B9 5SS
Research Site
Cambridge, CB2 0QQ
Research Site
Glasgow, G12 0YN
Research Site
Leicester, LE1 5WW
Research Site
London, EC1A 7BE
Research Site
Manchester, M20 4BX
Canada5 sites
Research Site
Brampton, Ontario, L6R 3J7
Research Site
Montreal, Quebec, H4A 3J1
Research Site
Québec, Quebec, G1R 2J6
Research Site
Toronto, Ontario, M4N 3M5
Research Site
Toronto, Ontario, M5G 1Z5
Greece5 sites
Research Site
Athens, 11526
Research Site
Athens, 11527
Research Site
Thessaloniki, 552 36
Research Site
Thessaloniki, 57001
Research Site
Thessaloniki, 57010
Philippines5 sites
Research Site
Davao City, 8000
Research Site
Manila, 1000
Research Site
Quezon, 1102
Research Site
Quezon, 1104
Research Site
San Juan City, 1500
Poland5 sites
Research Site
Katowice, 40-519
Research Site
Krakow, 30-727
Research Site
Lodz, 90-302
Research Site
Olsztyn, 10-357
Research Site
Poznan, 60-569
Thailand5 sites
Research Site
Bangkok, 10330
Research Site
Bangkok, 10400
Research Site
Bangkok, 10700
Research Site
Hat Yai, 90110
Research Site
Khon Kaen, 40002
Singapore2 sites
Research Site
Singapore, 168583
Research Site
Singapore, 308433
About this study
Official title: 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)
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).
Read the detailed description
This is a Phase III, open-label, 3-arm, multicenter study assessing the effects of Dato-DXd in combination with osimertinib or Dato-DXd monotherapy versus platinum-based doublet chemotherapy in participants with epidermal growth factor receptor gene mutation (EGFRm) locally advanced or metastatic non-small cell lung cancer (NSCLC) whose disease has progressed on prior osimertinib treatment.
Participants will be randomized in a 1:1:1 ratio to one of the following intervention groups:
- Dato-DXd + osimertinib combination therapy
- Dato-DXd monotherapy
- Platinum-based doublet chemotherapy
Participants will receive study intervention until Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) -defined radiological progression by the investigator, unacceptable toxicity, or other discontinuation criterion is met.
After study intervention discontinuation, all participants will undergo an end of treatment (EoT) visit within 35 days of discontinuation and will be followed up for safety assessments 28 (+ 7) days after their last dose of study intervention.
- Conditions
- Metastatic Non-small Cell Lung Cancer
- Being tested
- Dato-DXd, Osimertinib, Pemetrexed, Carboplatin, Cisplatin
- Keywords
- Epidermal growth factor receptor gene mutation, Standard of Care, Locally, advanced carcinoma, Metastatic carcinoma, Non-small cell lung cancer, Dato-dxd, Datopotamab deruxtecan, Osimertinib, Tagrisso, Pemetrexed, Carboplatin, Cisplatin
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dato-DXdDrug
Also called DS-1062a
Dato-DXd will be administered as IV infusion.
OsimertinibDrug
Also called Tagrisso, AZD9291
Osimertinib will be administered orally.
PemetrexedDrug
Pemetrexed will be administered as IV infusion.
CarboplatinDrug
Carboplatin will be administered as IV infusion.
CisplatinDrug
Cisplatin will be administered as IV infusion.
| Study group | Role | What they receive |
|---|---|---|
| Group 1: Dato-DXd + Osimertinib Combination Therapy | Experimental | Participants 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. Receives: Drug: Dato-DXd; Drug: Osimertinib |
| Group 2: Dato-DXd Monotherapy | Experimental | Participants 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. Receives: Drug: Dato-DXd |
| Group 3: Platinum-based Doublet Chemotherapy | Experimental | Participants 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. Receives: Drug: Pemetrexed; Drug: Carboplatin; Drug: Cisplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 2.5 years
Secondary outcomes (12)
Overall Survival (OS)
OS is defined as time from randomization until the date of death due to any cause.
Measured: Up to 3.5 years
Central Nervous System Progression-free Survival (CNS PFS)
CNS PFS is defined as the time from randomization to BICR confirmed progression in the CNS or death due to any cause, regardless of whether the participant withdraws from study therapy, receives other anti-cancer therapy, or clinically progresses prior to BICR confirmed CNS modified RECIST v1.1 progression.
Measured: Up to 2.5 years
Objective Response Rate (ORR)
ORR is defined as the percentage of participants who have a confirmed complete response (CR) or confirmed partial response (PR), as determined by BICR per RECIST v1.1.
Measured: Up to 2.5 years
Duration of Response (DoR)
DoR is defined as the time from the date of first documented response until date of documented progression per RECIST v1.1, as assessed by BICR or death due to any cause.
Measured: Up to 2.5 years
Progression-free Survival-2 (PFS-2)
PFS2 is defined as the time from randomization to the earliest of the progression event (following the initial investigator assessed progression), after first subsequent therapy, or death.
Measured: Up to 3.5 years
Objective Response Rate (ORR) Using CNS Modified RECIST v1.1
ORR is defined as the percentage of participants who have a confirmed CR or confirmed PR, using CNS modified RECIST v1.1.
Measured: Up to 2.5 years
Duration of Response (DoR) Using CNS Modified RECIST v1.1
DoR is defined as the time from the date of first documented response until date of documented progression or death due to any cause using CNS modified RECIST v1.1.
Measured: Up to 2.5 years
Time to Deterioration in Pulmonary Symptoms
Time to deterioration (in pulmonary symptoms [dyspnea, cough, and chest pain]) is defined as the time from randomization until the date of deterioration. Deterioration is defined as change from baseline that reaches a meaningful change threshold.
Measured: Up to 3.5 years
Time to Deterioration in Physical Functioning
Time to deterioration in physical functioning as measured by Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function short form 8c will be evaluated. Time to deterioration (in physical functionating) is defined as the time from randomization until the date of deterioration. Deterioration is defined as change from baseline that reaches a meaningful change threshold.
Measured: Up to 3.5 years
Time to Deterioration in Global Health Status (GHS)/Quality of Life (QoL)
Time to deterioration in GHS/QoL as measured by the GHS/QoL scale from EORTC IL172 will be reported. Time to deterioration (in GHS/QoL) is defined as the time from randomization until the date of deterioration. Deterioration is defined as change from baseline that reaches a meaningful change threshold.
Measured: Up to 3.5 years
Pharmacokinetics (PK) of Dato-DXd
Concentration of Dato-DXd, total anti-TROP2 antibody and DXd in plasma.
Measured: Up to 3.5 years
Immunogenicity of Dato-DXd
Presence of antidrug antibody (ADAs) for Dato-DXd (confirmatory results: positive or negative, titers).
Measured: Up to 3.5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 May 2024
- Study start4 Oct 2024
- Primary completion11 Jan 2027 (estimated)
- Study completion27 Sep 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metastatic Non-small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 768 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Daiichi Sankyo
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06417814
- Sponsor's protocol ID
- D516KC00001
- Other IDs
- 2024-511362-37-00
- Acronym
- TROPION-Lung15
- Status last verified
- Oct 2026
- First submitted
- 13 May 2024
- Last updated
- 15 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
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.
PubMed 41466843
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT06417814
- Acronym / sponsor ID
- TROPION-Lung15 / D516KC00001
- Conditions
- Metastatic Non-small Cell Lung Cancer
- Keywords
- Epidermal growth factor receptor gene mutation, Standard of Care, Locally, advanced carcinoma, Metastatic carcinoma, Non-small cell lung cancer, Dato-dxd, Datopotamab deruxtecan, Osimertinib
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 768 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Collaborators
- Daiichi Sankyo
- Study start
- 4 Oct 2024 (actual)
- Primary completion
- 11 Jan 2027 (estimated)
- Study completion
- 27 Sep 2028 (estimated)
- First posted
- 16 May 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
This is a Phase III, open-label, 3-arm, multicenter study assessing the effects of Dato-DXd in combination with osimertinib or Dato-DXd monotherapy versus platinum-based doublet chemotherapy in participants with epidermal growth factor receptor gene mutation (EGFRm) locally advanced or metastatic non-small cell lung cancer (NSCLC) whose disease has progressed on prior osimertinib treatment.
Participants will be randomized in a 1:1:1 ratio to one of the following intervention groups:
- Dato-DXd + osimertinib combination therapy
- Dato-DXd monotherapy
- Platinum-based doublet chemotherapy
Participants will receive study intervention until Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) -defined radiological progression by the investigator, unacceptable toxicity, or other discontinuation criterion is met.
After study intervention discontinuation, all participants will undergo an end of treatment (EoT) visit within 35 days of discontinuation and will be followed up for safety assessments 28 (+ 7) days after their last dose of study intervention.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Group 1: Dato-DXd + Osimertinib Combination Therapy | Experimental | Drug: Dato-DXd, Drug: OsimertinibParticipants 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 | Experimental | Drug: Dato-DXdParticipants 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 | Experimental | Drug: Pemetrexed, Drug: Carboplatin, Drug: CisplatinParticipants 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. |
Who may qualify
- Ages
- 18 to 130 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- - 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.
Key exclusion criteria (11 listed)
- - 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dato-DXdAlso: DS-1062aDato-DXd will be administered as IV infusion. | Drug | Group 1: Dato-DXd + Osimertinib Combination Therapy, Group 2: Dato-DXd Monotherapy |
| OsimertinibAlso: Tagrisso, AZD9291Osimertinib will be administered orally. | Drug | Group 1: Dato-DXd + Osimertinib Combination Therapy |
| PemetrexedPemetrexed will be administered as IV infusion. | Drug | Group 3: Platinum-based Doublet Chemotherapy |
| CarboplatinCarboplatin will be administered as IV infusion. | Drug | Group 3: Platinum-based Doublet Chemotherapy |
| CisplatinCisplatin will be administered as IV infusion. | Drug | Group 3: Platinum-based Doublet Chemotherapy |
Primary outcome
Progression free Survival (PFS)
Time frame: Up to 2.5 years
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.
12 secondary outcomes
Overall Survival (OS)
Time frame: Up to 3.5 years
Central Nervous System Progression-free Survival (CNS PFS)
Time frame: Up to 2.5 years
Objective Response Rate (ORR)
Time frame: Up to 2.5 years
Duration of Response (DoR)
Time frame: Up to 2.5 years
Progression-free Survival-2 (PFS-2)
Time frame: Up to 3.5 years
Objective Response Rate (ORR) Using CNS Modified RECIST v1.1
Time frame: Up to 2.5 years
Duration of Response (DoR) Using CNS Modified RECIST v1.1
Time frame: Up to 2.5 years
Time to Deterioration in Pulmonary Symptoms
Time frame: Up to 3.5 years
Time to Deterioration in Physical Functioning
Time frame: Up to 3.5 years
Time to Deterioration in Global Health Status (GHS)/Quality of Life (QoL)
Time frame: Up to 3.5 years
Pharmacokinetics (PK) of Dato-DXd
Time frame: Up to 3.5 years
Immunogenicity of Dato-DXd
Time frame: Up to 3.5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2026.
- Derived from this study: PubMed 41466843Tan 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.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
211 sites in 24 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Dato-DXd, Osimertinib and Pemetrexed in people with Metastatic Non-small Cell Lung Cancer, run by AstraZeneca at 211 sites in 24 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 15 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 211 sites in China, Japan, Spain, Italy, France and 19 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression free Survival (PFS) (time frame: Up to 2.5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06417814, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2026.