TROPION-Lung17 will measure the efficacy and safety of datopotamab deruxtecan (Dato-DXd) compared with docetaxel in patients with trophoblast cell surface protein 2 (TROP2) positive advanced or metastatic lung cancer without actionable genomic alterations (AGA).
TROPION-Lung17 is a phase III, 2-arm, randomised, open-label, multicentre study, assessing the efficacy and safety of Dato-DXd compared with docetaxel in participants with previously treated trophoblast cell surface protein 2 (TROP2) normalised membrane ratio (NMR) positive advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) without actionable genomic alterations (AGA), and to assess the clinical performance of the investigational in vitro diagnostic (IVD) device.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
400
Dato-DXd administered intravenously (IV)
Docetaxel administered intravenously (IV)
Progression-free survival (PFS)
PFS is defined as the time from randomization until radiological progression per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1) as assessed by Blinded Independent Central Review (BICR), or death due to any cause.
Time frame: Approximately 2.5 years
Overall survival (OS)
OS is defined as the time from randomization until the date of death due to any cause.
Time frame: Approximately 3.5 years
Objective response rate (ORR)
ORR is defined as the proportion of participants who have a confirmed complete response (CR) or confirmed partial response (PR), as determined by Blinded Independent Central Review (BICR) per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1).
Time frame: Approximately 2.5 years
Duration of response (DoR)
DoR is defined as the time from the date of first documented response until the date of documented progression per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1), as assessed by Blinded Independent Central Review (BICR) or death due to any cause.
Time frame: Approximately 2.5 years
Time to second progression or death (PFS2)
PFS2 is defined as the time from randomization until the earliest of the progression event (following the initial progression event), after first subsequent therapy, or death. The date of the second progression will be recorded by the Investigator in the electronic Case Report Form (eCRF) and defined according to local standard clinical practice based on radiological or clinical progression.
Time frame: Approximately 2.5 years
Exposure-efficacy relationship
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Research Site
Chandler, Arizona, United States
RECRUITINGResearch Site
Gilbert, Arizona, United States
RECRUITINGResearch Site
Goodyear, Arizona, United States
RECRUITINGResearch Site
Duarte, California, United States
RECRUITINGResearch Site
Irvine, California, United States
RECRUITINGResearch Site
La Jolla, California, United States
RECRUITINGResearch Site
Loma Linda, California, United States
NOT_YET_RECRUITINGResearch Site
Los Angeles, California, United States
NOT_YET_RECRUITINGResearch Site
San Diego, California, United States
NOT_YET_RECRUITINGResearch Site
Grand Junction, Colorado, United States
NOT_YET_RECRUITING...and 187 more locations
Evaluate the relationship between plasma concentrations of Dato-DXd (µg/mL) and efficacy endpoints (PFS, OS), as evaluated by cox-proportional hazard model.
Time frame: Approximately 2.5 years
Exposure-safety relationship
Evaluate the correlation between concentrations of Dato-DXd (µg/mL) and safety endpoints (including Gr3+AE, AESIs), as evaluated by logistic regression
Time frame: Approximately 2.5 years
Covariates effect on exposure
Evaluate the relationship between covariates (including but not limited to age, sex, body weight, race) and plasma concentrations of Dato-DXd (µg/mL) and/or DXd (ng/mL), as evaluated by population PK model
Time frame: Approximately 2.5 years
Immunogenicity of datopotamab deruxtecan (Dato-DXd)
Presence of antidrug antibodies (ADAs) for Dato-DXd.
Time frame: Approximately 2.5 years
Participant-reported lung cancer symptoms of non-small cell lung cancer (NSCLC)
Time to deterioration (TTD) in pulmonary symptoms (dyspnoea, cough, and chest pain) as measured by the Non-Small Cell Lung Cancer Symptom Assessment Questionnaire (NSCLC-SAQ). Scores range from a minimum of 0 to a maximum of 20, with higher scores indicating more symptom burden. TTD is defined as time from randomization to the date of first deterioration. Deterioration is defined as change from baseline that reaches an meaningful change threshold (MCT).
Time frame: Approximately 2.5 years
Participant-reported physical functioning
Time to deterioration (TTD) in physical functioning as measured by Patient-Reported Outcomes Measurement Information System (PROMIS) Short Form - Physical Function 8c. TTD is defined as time from randomization to the date of first deterioration. Deterioration is defined as change from baseline that reaches a meaningful change threshold (MCT).
Time frame: Approximately 2.5 years
Participant-reported global health status (GHS)/quality of life (QoL)
Time to deterioration (TTD) in GHS/QoL as measured by the European Organization for Research and Treatment of Cancer Item Library 172 (EORTC IL172). Scores range from a minimum of 0 to a maximum of 100, with higher scores indicating a better outcome. TTD is defined as time from the date of randomisation to the date of first deterioration. Deterioration is defined as change from baseline that reaches a meaningful change threshold (MCT).
Time frame: Approximately 2.5 years
Correlation of TROP2 expression at various cut offs with clinical response
Evaluate the relationship between TROP2 NMR expression and efficacy endpoints.
Time frame: Approximately 2.5 years
Diagnostic development and biomarker assay concordance analysis
Evaluate the relationship between TROP2 NMR status at a defined cutoff and efficacy endpoints, as determined by the diagnostic device.
Time frame: Approximately 2.5 years