protocolSection identificationModule nctId: NCT06350097, orgStudyIdInfo id: D516NC00001, briefTitle: 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, acronym: TROPION-Lung14, statusModule overallStatus: NOT_YET_RECRUITING, startDateStruct date: 2024-05-16, primaryCompletionDateStruct date: 2028-03-21, completionDateStruct date: 2032-05-25, studyFirstPostDateStruct date: 2024-04-05, lastUpdatePostDateStruct date: 2024-04-10, sponsorCollaboratorsModule leadSponsor name: AstraZeneca, class: INDUSTRY, collaborators name: Daiichi Sankyo, descriptionModule briefSummary: The purpose of this study is to evaluate efficacy and safety of osimertinib (tablet) in combination with Datopotamab Deruxtecan (i.v. infusion) compared with osimertinib (tablet) monotherapy as 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 9 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.Note: Participants on osimertinib treatment (osimertinib only arm or who have discontinued Datopotamab Deruxtecan 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, IP discontinuation or primary PFS DCO. Participants who are receiving osimertinib + Datopotamab Deruxtecan are still required to attend visit to perform assessment every 3 weeks (q3w) per SoA., conditionsModule conditions: Non-small Cell Lung Cancer, designModule studyType: INTERVENTIONAL, phases: PHASE3, designInfo allocation: RANDOMIZED, interventionModel: PARALLEL, primaryPurpose: TREATMENT, maskingInfo masking: NONE, enrollmentInfo count: 582, type: ESTIMATED, armsInterventionsModule interventions name: Osimertinib, interventions name: Datopotamab Deruxtecan, outcomesModule primaryOutcomes measure: To demonstrate the superiority of osimertinib in combination with Datopotamab Deruxtecan relative to osimertinib by assessment of PFS by BICR in all randomised participants., secondaryOutcomes measure: To demonstrate the superiority of osimertinib in combination with Datopotamab Deruxtecan relative to osimertinib by assessment of OS in all randomised participants., secondaryOutcomes measure: To demonstrate the effectiveness of osimertinib in combination with Datopotamab Deruxtecan relative to osimertinib by assessment of PFS on CNS metastases in participants with CNS metastases at baseline, secondaryOutcomes measure: To demonstrate the effectiveness of osimertinib in combination with Datopotamab Deruxtecan relative to osimertinib by assessment of PFS by investigator in all randomised participants., secondaryOutcomes measure: To demonstrate the effectiveness of osimertinib in combination with Datopotamab Deruxtecan relative to osimertinib by assessment of ORR in all randomised participants with measurable disease at baseline., secondaryOutcomes measure: To demonstrate the effectiveness of osimertinib in combination with Datopotamab Deruxtecan relative to osimertinib by assessment of DoR in all randomised participants with measurable disease at baseline., secondaryOutcomes measure: To demonstrate the effectiveness of osimertinib in combination with Datopotamab Deruxtecan relative to osimertinib on the prevention of CNS metastases, secondaryOutcomes measure: To demonstrate the effectiveness of osimertinib in combination with Datopotamab Deruxtecan relative to osimertinib by assessment of PFS2 in all randomised participants, secondaryOutcomes measure: To assess the PK of osimertinib and Datopotamab Deruxtecan, secondaryOutcomes measure: To investigate the immunogenicity of Datopotamab Deruxtecan, secondaryOutcomes measure: 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, secondaryOutcomes measure: 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, eligibilityModule sex: ALL, minimumAge: 18 Years, stdAges: ADULT, stdAges: OLDER_ADULT, contactsLocationsModule locations facility: Research Site, city: Clayton, zip: 3168, country: Australia, geoPoint lat: -37.91667, lon: 145.11667, locations facility: Research Site, city: Kogarah, zip: 2217, country: Australia, geoPoint lat: -33.98333, lon: 151.11667, locations facility: Research Site, city: Changchun, zip: 130000, country: China, geoPoint lat: 43.88, lon: 125.32278, locations facility: Research Site, city: Chongqing, zip: 400030, country: China, geoPoint lat: 29.56278, lon: 106.55278, locations facility: Research Site, city: Jinan, zip: 250021, country: China, geoPoint lat: 36.66833, lon: 116.99722, locations facility: Research Site, city: Jinan, zip: 250117, country: China, geoPoint lat: 36.66833, lon: 116.99722, locations facility: Research Site, city: Kunming, zip: 650118, country: China, geoPoint lat: 25.03889, lon: 102.71833, locations facility: Research Site, city: Linhai, zip: 318000, country: China, geoPoint lat: 28.85535, lon: 121.14469, locations facility: Research Site, city: Shanghai, zip: 200030, country: China, geoPoint lat: 31.22222, lon: 121.45806, locations facility: Research Site, city: Seoul, zip: 06351, country: Korea, Republic of, geoPoint lat: 37.566, lon: 126.9784, locations facility: Research Site, city: Seoul, zip: 120-752, country: Korea, Republic of, geoPoint lat: 37.566, lon: 126.9784, locations facility: Research Site, city: Seoul, zip: 13620, country: Korea, Republic of, geoPoint lat: 37.566, lon: 126.9784, locations facility: Research Site, city: Taipei City, zip: 106, country: Taiwan, geoPoint lat: 25.04776, lon: 121.53185, locations facility: Research Site, city: Taipei, zip: 10002, country: Taiwan, geoPoint lat: 25.04776, lon: 121.53185, locations facility: Research Site, city: Taoyuan, zip: 333, country: Taiwan, geoPoint lat: 24.95233, lon: 121.20193, hasResults: False