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 EGFR (eg, exon 19 deletion or exon 21 L858R, exon 21 L861Q, exon 18 G719X, or exon 20 S768I mutation), ALK, and ROS1 genomic alterations. Note: If test results for EGFR, ALK, and ROS1 are not available, participants are required to undergo prospective testing performed centrally for these genomic alterations in a Sponsor-designated central laboratory. * Has no known tumour genomic alterations in NTRK, BRAF V600, RET, MET exon 14 skipping, KRAS G12C, or HER2. Additionally, participants must not have known tumour genomic alteration of any other actionable driver oncogenes for which there are locally approved targeted first-line therapies. Note: Participants whose tumours harbour BRAF (exception V600) or KRAS (exception G12C) mutations are eligible for the study. * Prospectively assessed TROP2 NMR positive based on results from an appropriately validated investigational TROP2 RxDx device in a Sponsor- designated, regulatory compliant central laboratory. * 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 ILD/pneumonitis, 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. Examples of suspected ILD/pneumonitis by imaging include the presence of lung parenchymal fibrosis, such as combined pulmonary fibrosis and emphysema (CPFE), and any radiographic features consistent with interstitial lung abnormalities, including but not limited to, extensive ground glass opacities, reticular opacities, traction bronchiectasis, and honeycombing. * Has severe pulmonary function compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (eg, pulmonary emboli within 3 months of the study enrolment, severe asthma, severe COPD, restrictive lung disease, symptomatic pleural effusion, etc).
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. |
| 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). 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. 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. 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) |
| 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, France, 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