Non-small Cell Lung CancerPhase 3TROPION-Lung14NCT06350097

Phase III, Open-label Study of First-line Osimertinib With or Without Datopotamab Deruxtecan for EGFRm Locally Advanced or Metastatic Non-small Cell Lung Cancer

A Phase 3 study testing Osimertinib and Datopotamab Deruxtecan in people with Non-small Cell Lung Cancer, run by AstraZeneca at 167 sites in 19 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts

Official record

Search all trials

Trial summary

The purpose of this study is to evaluate efficacy and safety of osimertinib (tablet) in combination with Dato-DXd (i.v. infusion) compared with osimertinib (tablet) monotherapyas a first-line therapy in participants with locally advanced or metastatic EGFRm (Ex19del and/or L858R) NSCLC. Study details include: 1. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Non-small Cell Lung Cancer
What is being tested?: Osimertinib and Datopotamab Deruxtecan
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 582 participants
Where: 167 sitesin 19 countries
Study dates: 29 Apr 2024to 29 Aug 2031
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 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Age
Participant must be ≥ 18 years.
Type of Participant and Disease Characteristics
Histologically or cytologically documented nonsquamous NSCLC. NSCLC of mixed histology is allowed if adenocarcinoma is the predominant histology. Mixed small-cell lung cancer and NSCLC histology, and sarcomatoid variant of NSCLC is ineligible.
Stage IIIB or IIIC or Stage IV metastatic NSCLC or recurrent NSCLC (based on the American Joint Committee on Cancer Edition 8) not amenable to curative surgery or definitive chemoradiation at the time of randomisation.
Participants must not have received prior EGFR TKIs or other systemic therapy for Stage IIIB, IIIC or IV NSCLC.

Show all 11Show fewer

The tumour harbors at least 1 of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del or L858R), either alone or in combination with other genomic alterations, which may include EGFR T790M, assessed by a CLIA-certified (US sites) or an accredited (outside of the US) local laboratory or by central prospective tissue testing.
For participants enrolled in randomisation period, mandatory provision of an unstained, archival tumour tissue sample in a quantity sufficient to allow for central confirmation of the EGFR mutation status.
WHO performance status of 0 or 1.
At least one lesion not previously irradiated that qualifies as a RECIST 1.1 TL at baseline and can be accurately measured at baseline as ≥10 mm in the longest diameter (except lymph nodes, which must have short axis ≥15 mm) with CT or MRI and is suitable for accurate repeated measurements.
Adequate bone marrow reserve and organ function before the first dose of study intervention.

Who cannot join

As judged by the investigator, any evidence of diseases (such as severe or uncontrolled systemic diseases, including active bleeding diseases, history of allogenic organ transplant which, in the investigator's opinion, makes it undesirable for the participant to participate in the study or that would jeopardise compliance with the protocol.
Refractory nausea and vomiting, chronic gastrointestinal disease, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption, distribution, metabolism, or excretion of osimertinib.
History of another primary malignancy.
Spinal cord compression and/or unstable brain metastases.
Clinically significant corneal disease.
Has active or uncontrolled hepatitis B or C virus infection, as defined by Protocol.
Past medical history of ILD/penumonitis, including radiation pneumonitis (apart from radiation pneumonitis that did not require steroids), or drug-induced ILD/pneumonitis, or has suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.
Has clinically severe pulmonary function compromise resulting from intercurrent pulmonary illnesses.

Trial locations and contacts

167 sites in 19 countries. Contact the study team or a site near you to ask about taking part.

AstraZeneca Clinical Study Information Center contact

1-877-240-9479

information.center@astrazeneca.com

Country

City, postcode or hospital

Sites recruiting now only

167 sites in 19 countries

United States37 sites, 29 recruiting

Research Site
Bethesda, Maryland, 20817
Recruiting
Research Site
Bridgeton, Missouri, 63044
Withdrawn
Research Site
Brooklyn, New York, 11212
Recruiting
Research Site
Chicago, Illinois, 60611
Withdrawn
Research Site
Dallas, Texas, 75390
Withdrawn
Research Site
Detroit, Michigan, 48201
Recruiting
Research Site
Fairfax, Virginia, 22031
Recruiting
Research Site
Fort Belvoir, Virginia, 22060
Recruiting
Research Site
Fort Wayne, Indiana, 46845
Recruiting
Research Site
Fountain Valley, California, 92708
Suspended
Research Site
Hinsdale, Illinois, 60521
Recruiting
Research Site
Honolulu, Hawaii, 96819
Withdrawn
Research Site
Houston, Texas, 77030
Recruiting
Research Site
Houston, Texas, 77090
Withdrawn
Research Site
Jacksonville, Florida, 32256
Recruiting
Research Site
Las Vegas, Nevada, 89169
Recruiting
Research Site
Los Alamitos, California, 90720
Recruiting
Research Site
Los Angeles, California, 90017
Recruiting
Research Site
Los Angeles, California, 90033
Recruiting
Research Site
Midlothian, Virginia, 23114
Recruiting
Research Site
Milwaukee, Wisconsin, 53226
Recruiting
Research Site
New Haven, Connecticut, 06510
Recruiting
Research Site
New York, New York, 10065
Recruiting
Research Site
North Chicago, Illinois, 60064
Recruiting
Research Site
Ocala, Florida, 34474
Recruiting
Research Site
Orange, California, 92868
Recruiting
Research Site
Orange City, Florida, 32763
Recruiting
Research Site
Saint Paul, Minnesota, 55102
Recruiting
Research Site
San Diego, California, 92123
Recruiting
Research Site
Santa Monica, California, 90404
Recruiting
Research Site
Seattle, Washington, 98104
Withdrawn
Research Site
St Louis, Missouri, 63110
Recruiting
Research Site
Tacoma, Washington, 98405
Recruiting
Research Site
Walnut Creek, California, 94598
Recruiting
Research Site
Washington D.C., District of Columbia, 20037
Withdrawn
Research Site
Webster, Texas, 77598
Recruiting
Research Site
Woodway, Texas, 76712
Recruiting

Other trials in United States

China33 sites, 33 recruiting

Research Site
Beijing, 100029
Recruiting
Research Site
Beijing, 100034
Recruiting
Research Site
Beijing, 100142
Recruiting
Research Site
Changchun, 130000
Recruiting
Research Site
Changsha, 410013
Recruiting
Research Site
Chengdu, 610000
Recruiting
Research Site
Chengdu, 610042
Recruiting
Research Site
Chengdu, 610072
Recruiting
Research Site
Chongqing, 400030
Recruiting
Research Site
Chongqing, 402260
Recruiting
Research Site
Guangzhou, 510100
Recruiting
Research Site
Hangzhou, 310006
Recruiting
Research Site
Hangzhou, 31000
Recruiting
Research Site
Hangzhou, 310022
Recruiting
Research Site
Harbin, 150049
Recruiting
Research Site
Hefei, 230031
Recruiting
Research Site
Hefei, 230601
Recruiting
Research Site
Jinan, 250021
Recruiting
Research Site
Jinan, 250117
Recruiting
Research Site
Kunming, 650118
Recruiting
Research Site
Linhai, 317000
Recruiting
Research Site
Ningbo, 315010
Recruiting
Research Site
Shanghai, 200030
Recruiting
Research Site
Shanghai, 200433
Recruiting
Research Site
Shenyang, 110004
Recruiting
Research Site
Wenzhou, 325000
Recruiting
Research Site
Wuhan, 430022
Recruiting
Research Site
Wuhan, 430030
Recruiting
Research Site
Xi'an, 710061
Recruiting
Research Site
Xuzhou, 221000
Recruiting
Research Site
Yangzhou, 225001
Recruiting
Research Site
Zhengzhou, 450000
Recruiting
Research Site
Zhengzhou, 450008
Recruiting

Other trials in China

India11 sites, 5 recruiting

Research Site
Bangalore, 560027
Recruiting
Research Site
Delhi, 110085
Withdrawn
Research Site
Hyderabad, 500032
Recruiting
Research Site
Kolkata, 700054
Withdrawn
Research Site
Mysuru, 570017
Withdrawn
Research Site
Nagpur, 440001
Withdrawn
Research Site
Nashik, 422011
Recruiting
Research Site
New Delhi, 100049
Withdrawn
Research Site
New Delhi, 11029
Recruiting
Research Site
Vadodara, 391760
Recruiting
Research Site
Varanasi, 221005
Withdrawn

Other trials in India

Japan11 sites, 11 recruiting

Research Site
Chūōku, 104-0045
Recruiting
Research Site
Fukuoka, 812-8582
Recruiting
Research Site
Kashiwa, 277-8577
Recruiting
Research Site
Kōtoku, 135-8550
Recruiting
Research Site
Niigata, 951-8566
Recruiting
Research Site
Osaka, 541-8567
Recruiting
Research Site
Sakai, 590-0197
Recruiting
Research Site
Sapporo, 003-0804
Recruiting
Research Site
Sendai, 981-0914
Recruiting
Research Site
Wakayama, 641-8510
Recruiting
Research Site
Yokohama, 241-8515
Recruiting

Other trials in Japan

Germany9 sites, 8 recruiting

Research Site
Berlin, 13125
Recruiting
Research Site
Cologne, 51109
Recruiting
Research Site
Erfurt, 99089
Recruiting
Research Site
Frankfurt, 60488
Recruiting
Research Site
Göttingen, 37075
Withdrawn
Research Site
Immenhausen, 34376
Recruiting
Research Site
Kiel, 24105
Recruiting
Research Site
Mainz, 55131
Recruiting
Research Site
München, 81925
Recruiting

Other trials in Germany

South Korea6 sites

Research Site
Goyang-si, 410-769
Active, not recruiting
Research Site
Namdong-gu, 21565
Active, not recruiting
Research Site
Seoul, 03080
Active, not recruiting
Research Site
Seoul, 06351
Active, not recruiting
Research Site
Seoul, 120-752
Active, not recruiting
Research Site
Suwon, 16247
Active, not recruiting

Other trials in South Korea

Spain6 sites, 6 recruiting

Research Site
A Coruña, 15006
Recruiting
Research Site
Barcelona, 8036
Recruiting
Research Site
Granada, 18007
Recruiting
Research Site
Madrid, 28040
Recruiting
Research Site
Majadahonda, 28222
Recruiting
Research Site
Valencia, 46009
Recruiting

Other trials in Spain

Taiwan6 sites, 6 recruiting

Research Site
Taichung, 40705
Recruiting
Research Site
Tainan, 704
Recruiting
Research Site
Taipei, 10002
Recruiting
Research Site
Taipei, 106
Recruiting
Research Site
Taipei, TAIWAN
Recruiting
Research Site
Taoyuan, 333
Recruiting

Other trials in Taiwan

Turkey (Türkiye)6 sites, 4 recruiting

Research Site
Adapazarı, 54100
Recruiting
Research Site
Ankara, 06530
Recruiting
Research Site
Goztepe Istanbul
Withdrawn
Research Site
Izmir, 35100
Withdrawn
Research Site
Küçükçekmece, 34295
Recruiting
Research Site
Seyhan, 1060
Recruiting

Other trials in Turkey (Türkiye)

Vietnam6 sites

Research Site
Hà Nội, 100000
Active, not recruiting
Research Site
Hanoi, 100000
Active, not recruiting
Research Site
Ho Chi Minh City, 700000
Active, not recruiting
Research Site
Ho Chi Minh City, 70000
Active, not recruiting
Research Site
Ho Chi Minh City
Active, not recruiting
Research Site
Vinh, 460000
Active, not recruiting

Other trials in Vietnam

Australia5 sites, 5 recruiting

Research Site
Camperdown, 2050
Recruiting
Research Site
Clayton, 3168
Recruiting
Research Site
Kogarah, 2217
Recruiting
Research Site
South Brisbane, 4101
Recruiting
Research Site
Westmead, 2145
Recruiting

Other trials in Australia

Brazil5 sites, 5 recruiting

Research Site
Barretos, 14784-400
Recruiting
Research Site
Natal, 59075-740
Recruiting
Research Site
Porto Alegre, 91350-200
Recruiting
Research Site
Salvador, 41253-190
Recruiting
Research Site
São Paulo, 01246-000
Recruiting

Other trials in Brazil

Italy5 sites, 5 recruiting

Research Site
Milan, 20141
Recruiting
Research Site
Monza, 20900
Recruiting
Research Site
Orbassano, 10043
Recruiting
Research Site
Padova, 35128
Recruiting
Research Site
Parma, 43100
Recruiting

Other trials in Italy

Thailand5 sites

Research Site
Bangkok, 10400
Active, not recruiting
Research Site
Bangkok, 10700
Active, not recruiting
Research Site
Dusit, 10300
Active, not recruiting
Research Site
Hat Yai, 90110
Active, not recruiting
Research Site
Udon Thani, 41000
Active, not recruiting

Other trials in Thailand

France4 sites, 4 recruiting

Research Site
Angers, 49055
Recruiting
Research Site
Marseille, 13915
Recruiting
Research Site
Paris, 75005
Recruiting
Research Site
Strasbourg, 67091, Cedex
Recruiting

Other trials in France

Hong Kong4 sites, 4 recruiting

Research Site
Hong Kong, 999077
Recruiting
Research Site
Hong Kong
Recruiting
Research Site
Jordan, 999077
Recruiting
Research Site
Lai Chi Kok
Recruiting

Other trials in Hong Kong

Poland4 sites, 4 recruiting

Research Site
Bystra, 43-360
Recruiting
Research Site
Olsztyn, 10-357
Recruiting
Research Site
Poznan, 60-569
Recruiting
Research Site
Warsaw, 02-781
Recruiting

Other trials in Poland

Canada2 sites, 2 recruiting

Research Site
Edmonton, Alberta, T6G 1Z2
Recruiting
Research Site
Montreal, Quebec, H4A 3J1
Recruiting

Other trials in Canada

Puerto Rico2 sites, 2 recruiting

Research Site
Rio Piedras, 00935
Recruiting
Research Site
San Juan, 00918
Recruiting

Other trials in Puerto Rico

About this study

Official title: A Phase III, Open-label, Randomised Study of Osimertinib With or Without Datopotamab Deruxtecan (Dato-DXd), as First-line Treatment in Participants With Epidermal Growth Factor Receptor (EGFR) Mutation-positive, Locally Advanced or Metastatic Non-small Cell Lung Cancer

Study details include:

The study duration will be event-driven, with an estimated duration of approximately 8 years.
Participants may receive study treatment until disease progression, unacceptable toxicity, or other specific discontinuation criteria are met.
The visit frequency will be every 3 weeks during the treatment period.

Note: Participants on osimertinib treatment(osimertinib only arm or who have discontinued Dato-DXd while are still receiving osimertinib) are required to attend visits to perform assessments every 6 weeks from Cycle 7 until Cycle 17 and then visits every 12 weeks until disease progression or IP discontinuation. Participants who are receiving osimertinib + Dato-DXd are still required to attend visit to perform assessment every 3 weeks (q3w) per SoA.

Read the detailed description

This is a global Phase III, open-label, randomised, multicentre study assessing the efficacy and safety of osimertinib in combination with Datopotamab Deruxtecan compared with osimertinib in participants with locally advanced or metastatic EGFRm (Ex19del and/or L858R) NSCLC who have not received any prior therapy for advanced disease.

Conditions: Non-small Cell Lung Cancer
Being tested: Osimertinib, Datopotamab Deruxtecan
Keywords: Non-small Cell Lung Cancer, NSCLC, Epidermal Growth Factor Receptor (EGFR) Mutation-positive, Osimertinib, Dato-DXd, Datopotamab Deruxtecan, Tagrisso
Medical subject headings: Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

OsimertinibDrug
Also called Osimertinib: Tagrisso, AZD9291
Osimertinib 80 mg administered orally once daily (QD).
Datopotamab DeruxtecanDrug
Also called Dato-DXd, DS-1062a
Datopotamab Deruxtecan 6 mg/kg administered as an intravenous (i.v.) infusion every 3 weeks (q3w).

Study groups in NCT06350097
Study group	Role	What they receive
Arm 1: Osimertinib in combination with Datopotamab Deruxtecan	Experimental	Participants in this group will receive osimertinib 80 mg QD as oral tablet with Datopotamab Deruxtecan 6mg/kg as i.v. infusion q3w of Day 1 of every 21-day cycle. Receives: Drug: Osimertinib; Drug: Datopotamab Deruxtecan
Arm 2: Osimertinib monotherapy	Active comparator	Participants in this group will receive osimertinib 80 mg QD as oral tablet. Receives: Drug: Osimertinib

What is being measured

The primary outcome is the main question the study is designed to answer.

To demonstrate the superiority of osimertinib in combination with Datopotamab Deruxtecan relative to osimertinib by assessment of Progression Free Survival (PFS) by BICR in all randomised participants.
PFS is defined as time from randomisation until progression per RECIST 1.1 as assessed by BICR, or death due to any cause (in the absence of progression).
Measured: It is anticipated that it will be performed approximately 3 years after the first participant is randomised.

Secondary outcomes (11)

To demonstrate the superiority of osimertinib in combination with Datopotamab Deruxtecan relative to osimertinib by assessment of Overall Survival (OS) in all randomised participants.
OS defined as the time from randomisation until the date of death due to any cause.
Measured: It is anticipated that it will be performed approximately 7 years after the first participant has been randomised.
To demonstrate the effectiveness of osimertinib in combination with Datopotamab Deruxtecan relative to osimertinib by assessment of PFS on Central nervous system (CNS) metastases in participants with CNS metastases at baseline
Central nervous system progression-free survival (CNS PFS) is defined as the time from randomisation until the date of objective CNS progression assessed by CNS BICR or death (by any cause in absence of CNS progression).
Measured: It is anticipated that it will be performed approximately 3 years after the first participant is randomised.
To demonstrate the effectiveness of osimertinib in combination with Datopotamab Deruxtecan relative to osimertinib by assessment of PFS by investigator in all randomised participants.
PFS is defined as time from randomisation until progression per RECIST 1.1 as assessed by investigator, or death due to any cause (in the absence of progression).
Measured: It is anticipated that it will be performed approximately 3 years after the first participant is randomised.
To demonstrate the effectiveness of osimertinib in combination with Datopotamab Deruxtecan relative to osimertinib by assessment of Overall Response Rate (ORR) in all randomised participants with measurable disease at baseline.
ORR is defined as the proportion of participants who have a confirmed Complete Response (CR) or confirmed Partial Response (PR), as determined by BICR (and investigator) per RECIST 1.1.
Measured: It is anticipated that it will be performed approximately 3 years after the first participant is randomised.
To demonstrate the effectiveness of osimertinib in combination with Datopotamab Deruxtecan relative to osimertinib by assessment of Duration of Response (DoR) in all randomised participants with measurable disease at baseline.
DoR is defined as the time from the date of first documented confirmed response until date of documented progression per RECIST 1.1, as assessed by BICR (and investigator) assessment or death due to any cause.
The measure of interest is the median of DoR.
Measured: It is anticipated that it will be performed approximately 3 years after the first participant is randomised.
To demonstrate the effectiveness of osimertinib in combination with Datopotamab Deruxtecan relative to osimertinib on the prevention of CNS metastases
Neuro-radiologist assessments according to CNS RECIST 1.1 to determine the presence/absence of CNS lesions at progression in participants without CNS metastases at baseline.
Measured: It is anticipated that it will be performed approximately 3 years after the first participant is randomised.
To demonstrate the effectiveness of osimertinib in combination with Datopotamab Deruxtecan relative to osimertinib by assessment of PFS2 in all randomised participants
PFS2 will be defined as the time from randomisation to the earliest of the progression event (following the initial progression) subsequent to first subsequent anti-cancer therapy, or death.
Measured: It is anticipated that it will be analyzed by time of PFS primary which is about 3 years after the first participant has been randomised.
To assess the Pharmacokinetics (PK) of osimertinib and Datopotamab Deruxtecan
Concentration of osimertinib and its metabolite AZ5104, Datopotamab Deruxtecan, and DXd in plasma.
Measured: It is anticipated that it will be performed approximately 3 years after the first participant has been randomised.
To investigate the immunogenicity of Datopotamab Deruxtecan
Presence of ADAs for Datopotamab Deruxtecan (confirmatory results: positive or negative, titres, and neutralizing antibodies).
Measured: It is anticipated that it will be performed approximately 3 years after the first participant has been randomised, together with PFS primary.
To compare the local EGFR mutation test result used for patient selection with the retrospective central cobas® EGFR Mutation Test v2 results from baseline tumour samples
Concordance of EGFR mutation status between the local EGFR mutation test and the central cobas® EGFR Mutation Test v2 results from tumour samples with evaluable results.
Measured: It is anticipated that it will be performed approximately 3 years after the first participant is randomised.
To demonstrate the effectiveness of osimertinib in combination with Datopotamab Deruxtecan vs. osimertinib monotherapy based on the cobas® EGFR Mutation Test v2 plasma screening test result for Ex19del or L858R EGFR mutations
PFS by Investigator by plasma EGFR mutation status PFS is defined as time from randomisation until progression per RECIST 1.1 as assessed by investigator, or death due to any cause (in the absence of progression).
Measured: It is anticipated that it will be performed approximately 3 years after the first participant has been randomised, together with PFS primary.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

29 Apr 202429 Aug 2031

First posted5 Apr 2024
Study start29 Apr 2024
Primary completion21 Mar 2028 (estimated)
Study completion29 Aug 2031 (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 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: 582 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT06350097
Sponsor's protocol ID: D516NC00001
Other IDs: 2023-509883-89-00, 2023
Acronym: TROPION-Lung14
Status last verified: Aug 2026
First submitted: 2 Apr 2024
Last updated: 26 Aug 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 Vivli.org. All requests 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 shared.

Publications

Lu S, Pulla MP, Mascarenhas E, Tanizaki J, Kim HR, Liu Y, Feng S, Zhang B, Toms L, Yang JC, Goldberg SB. TROPION-Lung14 study protocol: a phase III study of osimertinib in combination with datopotamab deruxtecan versus osimertinib alone as first-line treatment for patients with EGFR-mutated locally advanced or metastatic non-small cell lung cancer. Ther Adv Med Oncol. 2026 May 20;18:17588359261430561. doi: 10.1177/17588359261430561. eCollection 2026.
PubMed 42182601

Interested in taking part?

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See sites and contacts

RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingObservational study
A Prospective ,Multicenter ,Non-interventional ,Real-world Study Observing Changes in Molecular Markers Osimertinib Targeted Therapy in EGFRm NSCLC
Non Small Cell Lung Cancer
RecruitingPhase 3
A Study Evaluating Sotorasib Platinum Doublet Combination Versus Pembrolizumab Platinum Doublet Combination as a Front-Line Therapy in Participants With Stage IV or Advanced Stage IIIB/C Nonsquamous Non-Small Cell Lung Cancers (CodeBreaK 202)
Non-Small Cell Lung Cancer (NSCLC)
Active, not recruitingPhase 2
Datopotamab Deruxtecan (Dato-DXd, DS-1062a) in Advanced and/or Unresectable Non-Small Cell Lung Cancer
Metastatic Lung Cancer, Advanced Non Small Cell Lung Cancer
Not yet recruitingPhase 1/2
STAR0602 With Nivolumab in Non Small Cell Lung Cancer and in Metastatic Castrate-Resistant Prostate Cancer, and STAR0602 Alone in Thymic Carcinoma
NSCLC, Non-Small Cell Lung Cancer

All Non-small Cell Lung Cancer trials

Study at a glance

From the registry record, last updated by the sponsor on 26 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase III, Open-label, Randomised Study of Osimertinib With or Without Datopotamab Deruxtecan (Dato-DXd), as First-line Treatment in Participants With Epidermal Growth Factor Receptor (EGFR) Mutation-positive, Locally Advanced or Metastatic Non-small Cell Lung Cancer
ClinicalTrials.gov ID: NCT06350097
Acronym / sponsor ID: TROPION-Lung14 / D516NC00001
Conditions: Non-small Cell Lung Cancer
Keywords: Non-small Cell Lung Cancer, NSCLC, Epidermal Growth Factor Receptor (EGFR) Mutation-positive, Osimertinib, Dato-DXd, Datopotamab Deruxtecan, Tagrisso
Phase: Phase 3
Study type: Interventional
Recruitment status: Recruiting
Enrolment: 582 participants (estimated)
Lead sponsor: AstraZenecaIndustry (pharma, biotech, devices)
Collaborators: Daiichi Sankyo
Study start: 29 Apr 2024 (actual)
Primary completion: 21 Mar 2028 (estimated)
Study completion: 29 Aug 2031 (estimated)
First posted: 5 Apr 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.

Study details include:

The study duration will be event-driven, with an estimated duration of approximately 8 years.
Participants may receive study treatment until disease progression, unacceptable toxicity, or other specific discontinuation criteria are met.
The visit frequency will be every 3 weeks during the treatment period.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Arm 1: Osimertinib in combination with Datopotamab Deruxtecan	Experimental	Drug: Osimertinib, Drug: Datopotamab DeruxtecanParticipants in this group will receive osimertinib 80 mg QD as oral tablet with Datopotamab Deruxtecan 6mg/kg as i.v. infusion q3w of Day 1 of every 21-day cycle.
Arm 2: Osimertinib monotherapy	Active comparator	Drug: OsimertinibParticipants in this group will receive osimertinib 80 mg QD as oral tablet.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (11 listed)

Age
Participant must be ≥ 18 years.
Type of Participant and Disease Characteristics
Histologically or cytologically documented nonsquamous NSCLC. NSCLC of mixed histology is allowed if adenocarcinoma is the predominant histology. Mixed small-cell lung cancer and NSCLC histology, and sarcomatoid variant of NSCLC is ineligible.
Stage IIIB or IIIC or Stage IV metastatic NSCLC or recurrent NSCLC (based on the American Joint Committee on Cancer Edition 8) not amenable to curative surgery or definitive chemoradiation at the time of randomisation.

Key exclusion criteria (8 listed)

As judged by the investigator, any evidence of diseases (such as severe or uncontrolled systemic diseases, including active bleeding diseases, history of allogenic organ transplant which, in the investigator's opinion, makes it undesirable for the participant to participate in the study or that would jeopardise compliance with the protocol.
Refractory nausea and vomiting, chronic gastrointestinal disease, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption, distribution, metabolism, or excretion of osimertinib.
History of another primary malignancy.
Spinal cord compression and/or unstable brain metastases.
Clinically significant corneal disease.

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
OsimertinibAlso: Osimertinib: Tagrisso, AZD9291Osimertinib 80 mg administered orally once daily (QD).	Drug	Arm 1: Osimertinib in combination with Datopotamab Deruxtecan, Arm 2: Osimertinib monotherapy
Datopotamab DeruxtecanAlso: Dato-DXd, DS-1062aDatopotamab Deruxtecan 6 mg/kg administered as an intravenous (i.v.) infusion every 3 weeks (q3w).	Drug	Arm 1: Osimertinib in combination with Datopotamab Deruxtecan

Primary outcome

To demonstrate the superiority of osimertinib in combination with Datopotamab Deruxtecan relative to osimertinib by assessment of Progression Free Survival (PFS) by BICR in all randomised participants.
Time frame: It is anticipated that it will be performed approximately 3 years after the first participant is randomised.
PFS is defined as time from randomisation until progression per RECIST 1.1 as assessed by BICR, or death due to any cause (in the absence of progression).

11 secondary outcomes

To demonstrate the superiority of osimertinib in combination with Datopotamab Deruxtecan relative to osimertinib by assessment of Overall Survival (OS) in all randomised participants.
Time frame: It is anticipated that it will be performed approximately 7 years after the first participant has been randomised.
To demonstrate the effectiveness of osimertinib in combination with Datopotamab Deruxtecan relative to osimertinib by assessment of PFS on Central nervous system (CNS) metastases in participants with CNS metastases at baseline
Time frame: It is anticipated that it will be performed approximately 3 years after the first participant is randomised.
To demonstrate the effectiveness of osimertinib in combination with Datopotamab Deruxtecan relative to osimertinib by assessment of PFS by investigator in all randomised participants.
Time frame: It is anticipated that it will be performed approximately 3 years after the first participant is randomised.
To demonstrate the effectiveness of osimertinib in combination with Datopotamab Deruxtecan relative to osimertinib by assessment of Overall Response Rate (ORR) in all randomised participants with measurable disease at baseline.
Time frame: It is anticipated that it will be performed approximately 3 years after the first participant is randomised.
To demonstrate the effectiveness of osimertinib in combination with Datopotamab Deruxtecan relative to osimertinib by assessment of Duration of Response (DoR) in all randomised participants with measurable disease at baseline.
Time frame: It is anticipated that it will be performed approximately 3 years after the first participant is randomised.
To demonstrate the effectiveness of osimertinib in combination with Datopotamab Deruxtecan relative to osimertinib on the prevention of CNS metastases
Time frame: It is anticipated that it will be performed approximately 3 years after the first participant is randomised.
To demonstrate the effectiveness of osimertinib in combination with Datopotamab Deruxtecan relative to osimertinib by assessment of PFS2 in all randomised participants
Time frame: It is anticipated that it will be analyzed by time of PFS primary which is about 3 years after the first participant has been randomised.
To assess the Pharmacokinetics (PK) of osimertinib and Datopotamab Deruxtecan
Time frame: It is anticipated that it will be performed approximately 3 years after the first participant has been randomised.
To investigate the immunogenicity of Datopotamab Deruxtecan
Time frame: It is anticipated that it will be performed approximately 3 years after the first participant has been randomised, together with PFS primary.
To compare the local EGFR mutation test result used for patient selection with the retrospective central cobas® EGFR Mutation Test v2 results from baseline tumour samples
Time frame: It is anticipated that it will be performed approximately 3 years after the first participant is randomised.
To demonstrate the effectiveness of osimertinib in combination with Datopotamab Deruxtecan vs. osimertinib monotherapy based on the cobas® EGFR Mutation Test v2 plasma screening test result for Ex19del or L858R EGFR mutations
Time frame: It is anticipated that it will be performed approximately 3 years after the first participant has been randomised, together with PFS primary.

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 26 Aug 2026.
Derived from this study: PubMed 42182601Lu S, Pulla MP, Mascarenhas E, Tanizaki J, Kim HR, Liu Y, Feng S, Zhang B, Toms L, Yang JC, Goldberg SB. TROPION-Lung14 study protocol: a phase III study of osimertinib in combination with datopotamab deruxtecan versus osimertinib alone as first-line treatment for patients with EGFR-mutated locally advanced or metastatic non-small cell lung cancer. Ther Adv Med Oncol. 2026 May 20;18:17588359261430561. doi: 10.1177/17588359261430561. eCollection 2026.
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 Vivli.org. All requests 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 shared.

Related trials for Non-small Cell Lung Cancer

RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingObservational study
A Prospective ,Multicenter ,Non-interventional ,Real-world Study Observing Changes in Molecular Markers Osimertinib Targeted Therapy in EGFRm NSCLC
Non Small Cell Lung Cancer
RecruitingPhase 3
A Study Evaluating Sotorasib Platinum Doublet Combination Versus Pembrolizumab Platinum Doublet Combination as a Front-Line Therapy in Participants With Stage IV or Advanced Stage IIIB/C Nonsquamous Non-Small Cell Lung Cancers (CodeBreaK 202)
Non-Small Cell Lung Cancer (NSCLC)
Active, not recruitingPhase 2
Datopotamab Deruxtecan (Dato-DXd, DS-1062a) in Advanced and/or Unresectable Non-Small Cell Lung Cancer
Metastatic Lung Cancer, Advanced Non Small Cell Lung Cancer
Not yet recruitingPhase 1/2
STAR0602 With Nivolumab in Non Small Cell Lung Cancer and in Metastatic Castrate-Resistant Prostate Cancer, and STAR0602 Alone in Thymic Carcinoma
NSCLC, Non-Small Cell Lung Cancer

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.

AstraZeneca Clinical Study Information Center contact

1-877-240-9479

information.center@astrazeneca.com

167 sites in 19 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Osimertinib and Datopotamab Deruxtecan in people with Non-small Cell Lung Cancer, run by AstraZeneca at 167 sites in 19 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 11 inclusion and 8 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: looking for participants now, as of the sponsor's last update on 26 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 167 sites in United States, China, India, Japan, Germany and 14 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?

Contact AstraZeneca Clinical Study Information Center (1-877-240-9479, information.center@astrazeneca.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

To demonstrate the superiority of osimertinib in combination with Datopotamab Deruxtecan relative to osimertinib by assessment of Progression Free Survival (PFS) by BICR in all randomised participants. (time frame: It is anticipated that it will be performed approximately 3 years after the first participant is randomised.). 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 NCT06350097, 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 26 Aug 2026.