Phase III, Open-label, Study of First-line Dato-DXd in Combination With Rilvegostomig for Advanced Non-squamous NSCLC With High PD-L1 Expression (TC ≥ 50%) and Without Actionable Genomic Alterations
TROPION-Lung10
A Phase III, Randomised, Open-label, Global Study of Datopotamab Deruxtecan (Dato-DXd) in Combination With Rilvegostomig or Rilvegostomig Monotherapy Versus Pembrolizumab Monotherapy for the First-line Treatment of Participants With Locally-advanced or Metastatic Non-squamous NSCLC With High PD-L1 Expression (TC ≥ 50%) and Without Actionable Genomic Alterations (TROPION-Lung10)
2 other identifiers
interventional
675
20 countries
274
Brief Summary
The purpose of this study is to evaluate efficacy and safety of Dato-DXd in combination with rilvegostomig or rilvegostomig monotherapy compared with pembrolizumab monotherapy as a first line therapy in participants with locally advanced or metastatic non-squamous NSCLC with high PD-L1 expression (TC ≥ 50%) and without actionable genomic alterations.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3 nonsmall-cell-lung-cancer
Started Apr 2024
Typical duration for phase_3 nonsmall-cell-lung-cancer
274 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 5, 2024
CompletedFirst Posted
Study publicly available on registry
April 10, 2024
CompletedStudy Start
First participant enrolled
April 11, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 28, 2029
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 28, 2029
March 16, 2026
March 1, 2026
5.7 years
April 5, 2024
March 13, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Progression-Free Survival (PFS) in TROP2 biomarker positive participants.
PFS is defined as time from randomisation until progression per RECIST 1.1 as assessed by BICR, or death due to any cause. The analysis will include all randomised participants, as randomised, regardless of whether the participant withdraws from randomised therapy, receives another anti-cancer therapy or clinically progresses prior to RECIST 1.1 progression, in the following population: • TROP2 biomarker positive population The measure of interest is the HR of PFS. PFS by investigator will be reported as a sensitivity analysis.
Approximately 4 years
Overall Survival (OS) in TROP2 biomarker positive participants.
OS is defined as the time from randomisation until the date of death due to any cause. The analysis will include all randomised participants, as randomised, regardless of whether the participant withdraws from randomised therapy or receives another anti-cancer therapy, in the following population: • TROP2 biomarker positive population The measure of interest is the HR of OS.
Approximately 6 years
Secondary Outcomes (9)
Progression-Free Survival (PFS) in the FAS population.
Approximately 4 years
Overall Survival (OS) in the FAS population.
Approximately 6 years
Assessment of Objective Response Rate (ORR) by BICR in TROP2 biomarker positive and FAS populations
Approximately 4 years
Assessment of Duration of Response (DoR) by BICR in TROP2 biomarker positive and FAS populations
Approximately 4 years
Participant-reported lung cancer symptoms of NSCLC and participant-reported GHS/QOL in participants treated with Dato-DXd in combination with rilvegostomig relative to pembrolizumab.
Approximately 6 years
- +4 more secondary outcomes
Other Outcomes (1)
Safety of Dato-DXd in combination with rilvegostomig and rilvegostomig monotherapy as compared with pembrolizumab.
Approximately 6 years
Study Arms (3)
Arm 1: Datopotamab Deruxtecan in Combination With Rilvegostomig
EXPERIMENTALParticipants in the Datopotamab Deruxtecan (Dato-DXd) in combination with Rilvegostomig group will receive Dato-DXd plus rilvegostomig as intravenous (IV) infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle.
Arm 2: Rilvegostomig Monotherapy
EXPERIMENTALParticipants in the rilvegostomig monotherapy group will receive rilvegostomig as intravenous (IV) infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle.
Arm 3: Pembrolizumab Monotherapy
ACTIVE COMPARATORParticipants in the pembrolizumab group will receive pembrolizumab as intravenous (IV) infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle.
Interventions
Datopotamab Deruxtecan IV (intravenous)
Rilvegostomig IV (intravenous)
Pembrolizumab IV (intravenous)
Eligibility Criteria
You may qualify if:
- Histologically or cytologically documented non-squamous NSCLC.
- Stage IIIB or IIIC or Stage IV metastatic NSCLC (according to Edition 8 of the AJCC staging manual) not amenable to curative surgery or definitive chemoradiation.
- Absence of sensitising EGFR mutations, and ALK and ROS1 rearrangements, and absence of documented local test result for any other known genomic alteration for which there are locally approved and available targeted first-line therapies.
- Must provide tumor sample to determine PD-L1 status, TROP2 status and other biomarkers.
- Known tumour PD-L1 expression status defined as TC ≥ 50%
- At least one lesion, not previously irradiated that qualifies as a RECIST 1.1 target lesion at baseline
- ECOG performance status of 0 or 1
- Adequate bone marrow reserve and organ function
You may not qualify if:
- Prior systemic therapy for advanced/metastatic NSCLC.
- Squamous cell histology, or predominantly squamous cell histology NSCLC; mixed small cell lung cancer; NSCLC histology, sarcomatoid variant.
- History of another primary malignancy within 3 years
- Active or prior documented autoimmune or inflammatory disorders (with exceptions)
- Any evidence of severe or uncontrolled disease that makes it undesirable for the participant to participate in the study or that would jeopardies compliance with the protocol.
- Has clinically significant third-space fluid retention (for example pleural effusion) and is not amenable for repeated drainage.
- History of any ILD/pneumonitis, including radiation pneumonitis (apart from radiation pneumonitis that did not require steroids), or drug-induced ILD/pneumonitis, has current or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.
- Has significant pulmonary function compromise, as determined by the investigator
- Spinal cord compression, or brain metastases unless participant treated and no longer symptomatic, radiologically stable, and who require no treatment with corticosteroids or anticonvulsants.
- History of leptomeningeal carcinomatosis
- Known clinically significant corneal disease
- Active infection with TB, HBV, HCV, Hepatitis A, or known HIV infection that is not well controlled
- History of active primary immunodeficiency
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AstraZenecalead
- Daiichi Sankyocollaborator
Study Sites (281)
Research Site
Anchorage, Alaska, 99508, United States
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Tucson, Arizona, 85719, United States
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Little Rock, Arkansas, 72205, United States
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Springdale, Arkansas, 72762, United States
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Anaheim, California, 92801, United States
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Beverly Hills, California, 90211, United States
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Fountain Valley, California, 92708, United States
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Newport Beach, California, 92663, United States
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Clermont, Florida, 34711, United States
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Gainesville, Florida, 32608, United States
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Miami Beach, Florida, 33140, United States
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Orange City, Florida, 32763, United States
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Orlando, Florida, 32806, United States
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Orlando, Florida, 32827, United States
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West Palm Beach, Florida, 33401, United States
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Atlanta, Georgia, 30303, United States
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Atlanta, Georgia, 30318, United States
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Atlanta, Georgia, 30322, United States
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Atlanta, Georgia, 30342, United States
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Hinsdale, Illinois, 60521, United States
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Noblesville, Indiana, 46062, United States
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Paducah, Kentucky, 42003, United States
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Annapolis, Maryland, 21401, United States
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Boston, Massachusetts, 02114, United States
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Boston, Massachusetts, 02215, United States
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Dearborn, Michigan, 48126, United States
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Farmington Hills, Michigan, 48334, United States
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Grand Rapids, Michigan, 49503, United States
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Traverse City, Michigan, 49684, United States
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Hattiesburg, Mississippi, 39401, United States
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Kansas City, Missouri, 64132, United States
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Bozeman, Montana, 59715, United States
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Grand Island, Nebraska, 68803, United States
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Omaha, Nebraska, 68130, United States
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Las Vegas, Nevada, 89102, United States
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Reno, Nevada, 89502, United States
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Voorhees Township, New Jersey, 08043, United States
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Stony Brook, New York, 11794, United States
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Greenville, North Carolina, 27834, United States
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Salisbury, North Carolina, 28144, United States
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Cincinnati, Ohio, 45219, United States
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Columbus, Ohio, 43210, United States
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Maumee, Ohio, 43537, United States
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Toledo, Ohio, 43623, United States
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Portland, Oregon, 97213, United States
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Greenville, South Carolina, 29607, United States
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Sioux Falls, South Dakota, 57105, United States
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Chattanooga, Tennessee, 37404, United States
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Knoxville, Tennessee, 37920, United States
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Fort Worth, Texas, 76104, United States
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Houston, Texas, 77030, United States
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Houston, Texas, 77030, United States
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Houston, Texas, 77090, United States
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Kingwood, Texas, 77339, United States
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Odessa, Texas, 79761, United States
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Fort Belvoir, Virginia, 22060, United States
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Leesburg, Virginia, 20176, United States
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Midlothian, Virginia, 23114, United States
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Richmond, Virginia, 23230, United States
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Tacoma, Washington, 98405, United States
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Vancouver, Washington, 98684, United States
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Wenatchee, Washington, 98801, United States
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Appleton, Wisconsin, 54911, United States
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Birtinya, 4575, Australia
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Blacktown, 2148, Australia
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Clayton, 3168, Australia
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Gosford, 2250, Australia
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Melbourne, 3000, Australia
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South Brisbane, QL 4101, Australia
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Wodonga, 3690, Australia
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Innsbruck, 6020, Austria
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Krems, 3500, Austria
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Linz, 4020, Austria
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Rankweil, 6830, Austria
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Vienna, 1140, Austria
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Vienna, 1210, Austria
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Wels, 4600, Austria
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Anderlecht, 1070, Belgium
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Bruges, 8000, Belgium
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Hasselt, 3500, Belgium
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La Louvière, 7100, Belgium
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Liège, 4000, Belgium
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Barretos, 14784-400, Brazil
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Curitiba, 80730-150, Brazil
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Florianópolis, 88034-000, Brazil
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Ipatinga, 35162-189, Brazil
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Natal, 59075-740, Brazil
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Porto Alegre, 91350-200, Brazil
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Rio de Janeiro, 22211-230, Brazil
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Santa Maria, 97015-450, Brazil
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São Paulo, 01221-020, Brazil
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Taubaté, 12030-200, Brazil
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Vancouver, British Columbia, VSZ 4E6, Canada
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Winnipeg, Manitoba, R3E 0V9, Canada
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St. John's, Newfoundland and Labrador, A1B 3V6, Canada
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London, Ontario, N6A 4L6, Canada
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Newmarket, Ontario, L3Y 2P9, Canada
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Oshawa, Ontario, L1G 2B9, Canada
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Toronto, Ontario, M4N 3M5, Canada
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Lévis, Quebec, G6V 0B8, Canada
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Montreal, Quebec, H3T 1E2, Canada
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Montreal, Quebec, H3T 1M5, Canada
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Montreal, Quebec, H4J 1C5, Canada
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Rimouski, Quebec, G5L 5T1, Canada
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Trois-Rivières, Quebec, G8Z 3R9, Canada
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Saskatoon, Saskatchewan, S7N 4H4, Canada
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Chicoutimi, G7H 5H6, Canada
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Beijing, 100142, China
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Beijing, 101149, 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, 610041, China
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Chongqing, 400030, China
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Fuzhou, 350014, China
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Guangzhou, 510080, China
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Hangzhou, 310006, China
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Hangzhou, 310016, 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, 250117, China
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Jining, 272011, China
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Kunming, 650118, China
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Lanzhou, 730000, China
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Linhai, 317000, China
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Linyi, 276001, China
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Nanjing, 210009, China
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Nanning, 530000, China
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Nanning, 530021, China
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Shanghai, 200030, China
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Shanghai, 200032, China
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Shanghai, 200433, China
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Shenyang, 110022, China
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Taiyuan, 030000, China
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Tianjin, 300060, China
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Wenzhou, 325000, China
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Wuhan, 430000, China
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Wuhan, 430010, 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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Yangzhou, 225001, China
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Zhengzhou, 450000, China
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Zhengzhou, 450008, China
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Berlin, 10249, Germany
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Bonn, 53113, Germany
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Düsseldorf, 40489, Germany
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Essen, 45136, Germany
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Freiburg im Breisgau, 79106, Germany
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Gauting, 82131, Germany
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Georgsmarienhütte, 49124, Germany
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Gera, 07548, Germany
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Gütersloh, 33332, Germany
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Hamburg, 20251, Germany
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Hamburg, 22087, Germany
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Heidelberg, 69126, Germany
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Kempten, 87439, Germany
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Koblenz, 56068, Germany
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Ludwigsburg, 71640, Germany
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München, 81925, Germany
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Nuremberg, 90419, Germany
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Potsdam, 14467, Germany
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Ravensburg, 88212, Germany
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Budapest, 1121, Hungary
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Gyöngyös, 3200, Hungary
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Gyöngyös - Mátraháza, 3200, Hungary
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Győr, 9024, Hungary
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Gyula, 5700, Hungary
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Kecskemét, 6000, Hungary
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Salgótarján, 3100, Hungary
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Szekszárd, 7100, Hungary
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Székesfehérvár, 8000, Hungary
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Törökbálint, 2045, Hungary
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Chennai, 600031, India
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Dwārka, 110075, India
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Jaipur, 302004, India
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Kolkata, 700099, India
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Marg Jaipur, 302004, India
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Nagpur, 440001, India
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Nashik, 422011, India
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New Delhi, 110085, India
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New Delhi, 11029, India
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Surat, 395002, India
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Thiruvananthapuram, 695011, India
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Bergamo, 24125, Italy
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Genoa, 16132, Italy
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Milan, 20141, Italy
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Milan, 20162, Italy
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Monza, 20052, Italy
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Padua, 35128, Italy
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Pavia, 27100, Italy
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Ravenna, 48100, Italy
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Roma, 00128, Italy
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Rozzano, 20089, Italy
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Bunkyō City, 113-8431, Japan
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Bunkyō City, 160-0023, Japan
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Fukuoka, 812-8582, Japan
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Fukuoka, 814-0180, Japan
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Hidaka-shi, 350-1298, Japan
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Hirakata-shi, 573-1191, Japan
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Hirosaki-shi, 036-8563, Japan
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Hiroshima, 730-8518, Japan
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Kanazawa, 920-8641, Japan
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Kashiwa, 227-8577, Japan
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Kawasaki-shi, 216-8511, Japan
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Kumamoto, 860-8556, Japan
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Matsusaka-shi, 515-8544, Japan
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Nagoya, 460-0001, Japan
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Niigata, 951-8566, Japan
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Okayama, 700-8558, Japan
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Osaka, 545-8586, Japan
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Osakasayama-shi, 589-8511, Japan
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Sagamihara-shi, 252-0375, Japan
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Sapporo, 003-0804, Japan
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Takaoka-shi, 933-8555, Japan
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Takatsuki-shi, 569-8686, Japan
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Tokushima, 770-8503, Japan
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Tokyo, 104-0045, Japan
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Utsunomiya, 320-0834, Japan
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Yokohama, 221-0855, Japan
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Olsztyn, 10-357, Poland
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Poznan, 60-569, Poland
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Przemyśl, 37-700, Poland
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Warsaw, 01-138, Poland
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Warsaw, 02-781, Poland
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San Juan, 00909, Puerto Rico
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Changwon, 51353, South Korea
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Incheon, 21565, South Korea
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Seongnam-si, 13496, South Korea
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Seoul, 03080, South Korea
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Seoul, 03722, South Korea
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Suwon, 16247, South Korea
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Suwon, 16499, South Korea
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Alicante, 03010, Spain
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Barcelona, 08003, Spain
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Barcelona, 08036, Spain
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Barcelona, 08041, Spain
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Jerez de la Frontera, 11407, Spain
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Reus,Tarragona, 43204, Spain
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Salamanca, 37007, Spain
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Kaohsiung City, 80756, Taiwan
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New Taipei City, 220, Taiwan
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Taichung, 40447, Taiwan
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Taichung, 40705, Taiwan
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Tainan, 704, Taiwan
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Taipei, 0116, Taiwan
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Taipei, 10002, Taiwan
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Taipei, 112, Taiwan
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Taipei, TAIWAN, Taiwan
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Taoyuan District, 333, Taiwan
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Bangkok, 10400, Thailand
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Hat Yai, 90110, Thailand
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Muang, 22000, Thailand
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Mueang, 20000, Thailand
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Mueang, 32000, Thailand
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Adapazarı, 54100, Turkey (Türkiye)
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Ankara, 06560, Turkey (Türkiye)
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Ankara, 6200, Turkey (Türkiye)
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Antalya, 07070, Turkey (Türkiye)
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Diyarbakır, 21280, Turkey (Türkiye)
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Istanbul, 34030, Turkey (Türkiye)
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Istanbul, 34890, Turkey (Türkiye)
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Cheltenham, GL53 7AN, United Kingdom
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Inverness, IV2 3UJ, United Kingdom
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London, SE1 9RT, United Kingdom
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London, SW10 9NH, United Kingdom
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London, SW17 0QT, United Kingdom
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Preston, PR2 9HT, United Kingdom
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Truro, TR1 3LJ, United Kingdom
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Da Nang, 550000, Vietnam
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Hanoi, 100000, Vietnam
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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, 700000, Vietnam
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Ho Chi Minh City, 700000, Vietnam
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Huế, 530000, Vietnam
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Vinh, 460000, Vietnam
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Vĩnh Yên, 280000, Vietnam
Related Publications (1)
Newsom-Davis T, Melosky B, Heist RS, Lu S, Pasello G, Chen X, Stachowiak M, Lyfar P, Forcina A, Ramalingam SS. TROPION-Lung10: a phase 3 study of datopotamab deruxtecan and rilvegostomig in patients with treatment-naive locally advanced or metastatic nonsquamous non-small cell lung cancer with high PD-L1 expression and without actionable genomic alterations. Front Oncol. 2026 Jan 26;15:1721624. doi: 10.3389/fonc.2025.1721624. eCollection 2025.
PMID: 41669261DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Suresh S. Ramalingam, MD
Emory University, Atlanta, Georgia, United States of America.
Central Study Contacts
AstraZeneca Clinical Study Information Center
CONTACT
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- SINGLE
- Who Masked
- OUTCOMES ASSESSOR
- Masking Details
- Open-label, sponsor-blinded
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 5, 2024
First Posted
April 10, 2024
Study Start
April 11, 2024
Primary Completion (Estimated)
December 28, 2029
Study Completion (Estimated)
December 28, 2029
Last Updated
March 16, 2026
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- Time Frame
- AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
- Access Criteria
- When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure