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
TROPION-Lung14
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
2 other identifiers
interventional
582
19 countries
166
Brief 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.The study duration will be event-driven, with an estimated duration of approximately 8 years.
- 2.Participants may receive study treatment until disease progression, unacceptable toxicity, or other specific discontinuation criteria are met.
- 3.The visit frequency will be every 3 weeks during the treatment period.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3 nonsmall-cell-lung-cancer
Started Apr 2024
Longer than P75 for phase_3 nonsmall-cell-lung-cancer
166 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
April 2, 2024
CompletedFirst Posted
Study publicly available on registry
April 5, 2024
CompletedStudy Start
First participant enrolled
April 29, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 21, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
August 29, 2031
May 6, 2026
April 1, 2026
3.9 years
April 2, 2024
May 4, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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).
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.
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
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.
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.
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.
It is anticipated that it will be performed approximately 3 years after the first participant is randomised.
- +6 more secondary outcomes
Study Arms (2)
Arm 1: Osimertinib in combination with Datopotamab Deruxtecan
EXPERIMENTALParticipants 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 COMPARATORParticipants in this group will receive osimertinib 80 mg QD as oral tablet.
Interventions
Osimertinib 80 mg administered orally once daily (QD).
Datopotamab Deruxtecan 6 mg/kg administered as an intravenous (i.v.) infusion every 3 weeks (q3w).
Eligibility Criteria
You may qualify if:
- 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.
- 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.
You may not qualify if:
- 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, as defined by Protocol.
- 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.
- Pulmonary embolism within 3 months of the study enrolment or has severe pulmonary function compromise.
- Has clinically severe pulmonary function compromise resulting from intercurrent pulmonary illnesses.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AstraZenecalead
- Daiichi Sankyocollaborator
Study Sites (166)
Research Site
Fountain Valley, California, 92708, United States
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Los Alamitos, California, 90720, United States
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Los Angeles, California, 90017, United States
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Los Angeles, California, 90033, United States
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Orange, California, 92868, United States
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San Diego, California, 92123, United States
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Santa Monica, California, 90404, United States
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Walnut Creek, California, 94598, United States
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New Haven, Connecticut, 06510, United States
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Washington D.C., District of Columbia, 20037, United States
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Jacksonville, Florida, 32256, United States
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Ocala, Florida, 34474, United States
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Orange City, Florida, 32763, United States
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Honolulu, Hawaii, 96819, United States
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Chicago, Illinois, 60611, United States
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Hinsdale, Illinois, 60521, United States
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North Chicago, Illinois, 60064, United States
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Fort Wayne, Indiana, 46845, United States
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Bethesda, Maryland, 20817, United States
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Detroit, Michigan, 48201, United States
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Saint Paul, Minnesota, 55102, United States
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Bridgeton, Missouri, 63044, United States
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St Louis, Missouri, 63110, United States
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Las Vegas, Nevada, 89169, United States
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Brooklyn, New York, 11212, United States
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New York, New York, 10065, United States
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Dallas, Texas, 75390, United States
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Houston, Texas, 77030, United States
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Houston, Texas, 77090, United States
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Webster, Texas, 77598, United States
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Woodway, Texas, 76712, United States
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Fairfax, Virginia, 22031, United States
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Fort Belvoir, Virginia, 22060, United States
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Midlothian, Virginia, 23114, United States
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Seattle, Washington, 98104, United States
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Milwaukee, Wisconsin, 53226, United States
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Camperdown, 2050, Australia
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Clayton, 3168, Australia
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Kogarah, 2217, Australia
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South Brisbane, 4101, Australia
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Westmead, 2145, Australia
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Barretos, 14784-400, Brazil
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Natal, 59075-740, Brazil
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Porto Alegre, 91350-200, Brazil
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Salvador, 41253-190, Brazil
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São Paulo, 01246-000, Brazil
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Edmonton, Alberta, T6G 1Z2, Canada
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Montreal, Quebec, H4A 3J1, Canada
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Beijing, 100029, China
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Beijing, 100034, China
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Beijing, 100142, China
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Changchun, 130000, China
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Changsha, 410013, China
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Chengdu, 610000, China
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Chengdu, 610042, China
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Chengdu, 610072, China
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Chongqing, 400030, China
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Chongqing, 402260, China
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Guangzhou, 510100, China
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Hangzhou, 310006, China
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Hangzhou, 31000, China
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Hangzhou, 310022, China
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Harbin, 150049, China
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Hefei, 230031, China
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Hefei, 230601, China
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Jinan, 250021, China
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Jinan, 250117, China
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Kunming, 650118, China
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Linhai, 317000, China
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Ningbo, 315010, China
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Shanghai, 200030, China
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Shanghai, 200433, China
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Shenyang, 110004, China
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Wenzhou, 325000, China
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Wuhan, 430022, China
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Wuhan, 430030, China
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Xi'an, 710061, China
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Xuzhou, 221000, China
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Yangzhou, 225001, China
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Zhengzhou, 450000, China
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Zhengzhou, 450008, China
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Angers, 49055, France
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Marseille, 13915, France
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Paris, 75005, France
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Strasbourg, 67091, Cedex, France
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Berlin, 13125, Germany
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Cologne, 51109, Germany
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Erfurt, 99089, Germany
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Frankfurt, 60488, Germany
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Göttingen, 37075, Germany
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Immenhausen, 34376, Germany
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Kiel, 24105, Germany
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Mainz, 55131, Germany
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München, 81925, Germany
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Hong Kong, 999077, Hong Kong
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Hong Kong, Hong Kong
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Jordan, 999077, Hong Kong
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Lai Chi Kok, Hong Kong
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Bangalore, 560027, India
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Delhi, 110085, India
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Hyderabad, 500032, India
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Kolkata, 700054, India
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Mysuru, 570017, India
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Nagpur, 440001, India
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Nashik, 422011, India
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New Delhi, 100049, India
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New Delhi, 11029, India
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Vadodara, 391760, India
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Varanasi, 221005, India
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Milan, 20141, Italy
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Monza, 20900, Italy
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Orbassano, 10043, Italy
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Padova, 35128, Italy
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Parma, 43100, Italy
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Chūōku, 104-0045, Japan
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Fukuoka, 812-8582, Japan
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Kashiwa, 277-8577, Japan
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Kōtoku, 135-8550, Japan
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Niigata, 951-8566, Japan
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Osaka, 541-8567, Japan
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Sakai, 590-0197, Japan
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Sapporo, 003-0804, Japan
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Sendai, 981-0914, Japan
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Wakayama, 641-8510, Japan
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Yokohama, 241-8515, Japan
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Bystra, 43-360, Poland
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Olsztyn, 10-357, Poland
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Poznan, 60-569, Poland
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Warsaw, 02-781, Poland
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Rio Piedras, 00935, Puerto Rico
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San Juan, 00918, Puerto Rico
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Goyang-si, 410-769, South Korea
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Namdong-gu, 21565, South Korea
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Seoul, 03080, South Korea
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Seoul, 06351, South Korea
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Seoul, 120-752, South Korea
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Suwon, 16247, South Korea
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A Coruña, 15006, Spain
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Barcelona, 8036, Spain
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Granada, 18007, Spain
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Madrid, 28040, Spain
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Majadahonda, 28222, Spain
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Valencia, 46009, Spain
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Taichung, 40705, Taiwan
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Tainan, 704, Taiwan
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Taipei, 10002, Taiwan
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Taipei, 106, Taiwan
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Taipei, TAIWAN, Taiwan
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Taoyuan, 333, Taiwan
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Bangkok, 10400, Thailand
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Bangkok, 10700, Thailand
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Dusit, 10300, Thailand
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Hat Yai, 90110, Thailand
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Udon Thani, 41000, Thailand
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Adapazarı, 54100, Turkey (Türkiye)
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Ankara, 06530, Turkey (Türkiye)
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Goztepe Istanbul, Turkey (Türkiye)
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Izmir, 35100, Turkey (Türkiye)
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Küçükçekmece, 34295, Turkey (Türkiye)
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Seyhan, 1060, Turkey (Türkiye)
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Hanoi, 100000, Vietnam
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Hà Nội, 100000, Vietnam
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Ho Chi Minh City, 700000, Vietnam
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Ho Chi Minh City, 70000, Vietnam
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Ho Chi Minh City, Vietnam
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Vinh, 460000, Vietnam
MeSH Terms
Conditions
Interventions
Condition 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
April 2, 2024
First Posted
April 5, 2024
Study Start
April 29, 2024
Primary Completion (Estimated)
March 21, 2028
Study Completion (Estimated)
August 29, 2031
Last Updated
May 6, 2026
Record last verified: 2026-04
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 PhRMA 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. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
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.