Non-small Cell Lung Cancer (NSCLC)
Conditions
Keywords
TROPION-Lung17, Non-small cell lung cancer (NSCLC), Advanced non-squamous NSCLC, Metastatic non-squamous NSCLC, Datopotamab deruxtecan (Dato-DXd; DS-1062a), Docetaxel, Trophoblast cell surface protein 2 (TROP2), Normalised membrane ratio (NMR)
Brief summary
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).
Detailed description
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.
Interventions
Dato-DXd administered intravenously (IV)
DRUGDocetaxel
Docetaxel administered intravenously (IV)
Sponsors
AstraZeneca
Daiichi Sankyo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
TROPION-Lung17 is an open-label study; however, the study will be conducted as 'Sponsor-blind'.
Intervention model description
Arm A: Datopotamab deruxtecan monotherapy Arm B: Docetaxel monotherapy
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Pathologically documented Stage IIIB, IIIC, or Stage IV non-squamous non-small cell lung cancer (NSCLC) without actionable genomic alterations (AGA) at the time of randomisation and meets the criteria for NSCLC: * Participants must have documented negative test results for epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), and ROS proto-oncogene 1 (ROS1) genomic alterations. * Has no known tumour genomic alterations in neurotrophic tyrosine receptor kinase (NTRK), proto-oncogene B-raf (BRAF), rearranged during transfection (RET), mesenchymal-epithelial transition (MET) exon 14 skipping, Kirsten rat sarcoma viral oncogene homolog (KRAS) G12C, human epidermal growth factor receptor 2 (HER2) or any other actionable driver oncogenes for which there are locally approved and available targeted first-line therapies. * Prospectively assessed trophoblast cell surface protein 2 (TROP2) normalised membrane ratio (NMR) positive. * Documentation of radiographic disease progression while on or after receiving the most recent treatment regimen for advanced or metastatic NSCLC. * Participants must have received platinum based chemotherapy (PBC) in combination with anti-programmed death-protein 1 (anti-PD-1)/anti-programmed death-ligand 1 (anti-PD-L1) monoclonal antibody (mAb) as the only prior line of therapy or received PBC and anti-PD-1/anti-PD-L1 monoclonal antibody (in either order) sequentially as the only 2 prior lines of therapy. * Provision of acceptable formalin fixed and paraffin embedded (FFPE) tumour sample for assessment of TROP2. * At least one lesion not previously irradiated that qualifies as a Response Evaluation Criteria in Solid Tumours, Version 1.1 (RECIST 1.1) target lesion (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 computed tomography (CT) or magnetic resonance imaging (MRI) and is suitable for accurate repeated measurements. * Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1. * Adequate bone marrow reserve and organ function within 7 days before randomisation.
Exclusion criteria
* Squamous, mixed NSCLC, or small cell lung cancer (SCLC) histology. * NSCLC disease that is eligible for definitive local therapy alone. * History of another primary malignancy other than NSCLC, except for malignancy treated with curative intent with no known active disease within 3 years before randomisation and of low potential risk for recurrence. * Spinal cord compression or brain metastases, unless asymptomatic, stable, and not requiring treatment with corticosteroids or anticonvulsants for at least 7 days prior to randomisation. * Clinically significant corneal disease. * Has active or uncontrolled hepatitis B or C virus infection. * Known human immunodeficiency virus (HIV) infection that is not well controlled. * Uncontrolled infection requiring intravenous (IV) antibiotics, antivirals, or antifungals. * History of non-infectious interstitial lung disease (ILD)/pneumonitis including radiation pneumonitis that required steroids, has current ILD/pneumonitis, or has suspected ILD/pneumonitis that cannot be ruled out by imaging at screening. * Severe pulmonary function compromise per Investigator discretion.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival (PFS) | Approximately 2.5 years | 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. |
| Overall survival (OS) | Approximately 3.5 years | OS is defined as the time from randomization until the date of death due to any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate (ORR) | Approximately 2.5 years | 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). |
| Duration of response (DoR) | Approximately 2.5 years | 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 to second progression or death (PFS2) | Approximately 2.5 years | 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. |
| Exposure-efficacy relationship | Approximately 2.5 years | Evaluate the relationship between plasma concentrations of Dato-DXd (µg/mL) and efficacy endpoints (PFS, OS), as evaluated by cox-proportional hazard model. |
| Exposure-safety relationship | Approximately 2.5 years | Evaluate the correlation between concentrations of Dato-DXd (µg/mL) and safety endpoints (including Gr3+AE, AESIs), as evaluated by logistic regression |
| Covariates effect on exposure | Approximately 2.5 years | 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 |
| Immunogenicity of datopotamab deruxtecan (Dato-DXd) | Approximately 2.5 years | Presence of antidrug antibodies (ADAs) for Dato-DXd. |
| Participant-reported lung cancer symptoms of non-small cell lung cancer (NSCLC) | Approximately 2.5 years | 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). |
| Participant-reported physical functioning | Approximately 2.5 years | 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). |
| Participant-reported global health status (GHS)/quality of life (QoL) | Approximately 2.5 years | 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). |
| Correlation of TROP2 expression at various cut offs with clinical response | Approximately 2.5 years | Evaluate the relationship between TROP2 NMR expression and efficacy endpoints. |
| Diagnostic development and biomarker assay concordance analysis | Approximately 2.5 years | Evaluate the relationship between TROP2 NMR status at a defined cutoff and efficacy endpoints, as determined by the diagnostic device. |
Countries
Australia, Austria, Belgium, Brazil, Canada, China, Germany, Hungary, India, Italy, Japan, Poland, South Korea, Spain, Taiwan, Thailand, Turkey (Türkiye), United Kingdom, United States, Vietnam
Contacts
CONTACTAstraZeneca Clinical Study Information Center
Outcome results
None listed