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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
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.
Study details:
This is a Phase III, randomized, 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.
Eligibility criteria
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
Inclusion criteria
Exclusion criteria
Eligibility
Age eligible for study : 18 and older
Healthy volunteers accepted : No
Gender eligible for study: All
Things to know
Study dates
Study start: 2024-04-11
Primary completion: 2028-04-27
Study completion finish: 2030-05-24
Study type
TREATMENT
Phase
PHASE3
Trial ID
NCT06357533
Intervention or treatment
DRUG: Datopotamab Deruxtecan
DRUG: Rilvegostomig
DRUG: Pembrolizumab
Conditions
- • Non-Small Cell Lung Cancer
Find a site
Closest Location:
Research Site
Research sites nearby
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Research Site
Clayton, Not Specified, Australia
Research Site
Melbourne, Not Specified, Australia
Research Site
South Brisbane, Not Specified, Australia
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Participant Group/Arm | Intervention/Treatment |
---|---|
EXPERIMENTAL: Arm 1: Dato-DXd in Combination With Rilvegostomig
| DRUG: Datopotamab Deruxtecan
|
EXPERIMENTAL: Arm 2: Rilvegostomig Monotherapy
| DRUG: Rilvegostomig
|
ACTIVE_COMPARATOR: Arm 3: Pembrolizumab Monotherapy
| DRUG: Pembrolizumab
|
What is the study measuring?
Primary outcome
Primary Outcome Measure | Primary Outcome Description | Primary Outcome Time Frame |
---|---|---|
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 outcome
Secondary Outcome Measure | Secondary Outcome Description | Secondary Outcome Time Frame |
---|---|---|
Progression-Free Survival (PFS) in the intent-to-treat (ITT) population. | 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: • ITT 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 the intent-to-treat (ITT) population. | 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: • ITT population The measure of interest is the HR of OS. | Approximately 6 years |
Objective Response Rate (ORR) | ORR is defined as the proportion of participants who have a CR or PR, as determined by BICR per RECIST 1.1. The analyses will include all randomised participants, as randomised, with measurable disease at baseline, in the following populations: * TROP2 biomarker positive population * ITT population Data obtained from randomisation up until progression, or the last evaluable assessment in the absence of progression, will be included in the assessment of ORR, regardless of whether the participant withdraws from therapy. Participants who go off treatment without a response or progression, receive a subsequent therapy, and then respond will not be included as responders in the ORR. The measure of interest is the OR of the ORR. ORR by investigator will be reported as a sensitivity analysis. | Approximately 4 years |
Duration of Response (DoR) | DoR is defined as the time from the date of first documented response until date of documented progression per RECIST 1.1, as assessed by BICR and investigator assessment or death due to any cause. The analyses will include all randomised participants who have a response, 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 populations: * TROP2 biomarker positive population * ITT population The measure of interest is the median of DoR. DoR by investigator will be reported as a sensitivity analysis. | Approximately 4 years |
Participant-reported lung cancer symptoms of NSCLC in participants treated with Dato-DXd in combination with rilvegostomig relative to pembrolizumab. | Time to deterioration in pulmonary symptoms (dyspnoea, cough, and chest pain) as measured by the NSCLC-SAQ. Time to deterioration in overall lung cancer symptoms as measured by the NSCLC-SAQ. Time to deterioration is defined as the time from randomisation until the date of deterioration. Deterioration is defined as change from baseline that reaches a clinically meaningful deterioration threshold. The analyses will include all randomised participants, in the following populations: * TROP2 biomarker positive population * ITT population The measure of interest is the HR of time to deterioration in pulmonary symptoms and the HR of time to deterioration in overall lung cancer symptoms. | Approximately 6 years |
Participant-reported physical functioning in participants treated with Dato DXd in combination with rilvegostomig relative to pembrolizumab. | Time to deterioration in physical functioning as measured by PROMIS Physical Function short form 8c. Time to deterioration is defined as the time from randomisation until the date of deterioration. Deterioration is defined as change from baseline that reaches a clinically meaningful deterioration threshold. The analyses will include all randomised participants, in the following populations: * TROP2 biomarker positive population * ITT population The measure of interest is the HR of time to deterioration in physical functioning. | Approximately 6 years |
Participant-reported GHS/QoL in participants treated with Dato-DXd in combination with rilvegostomig relative to pembrolizumab. | Time to deterioration in GHS/QoL as measured by the GHS/QoL scale from EORTC IL172. Time to deterioration is defined as time from the date of randomisation to the date of deterioration. Deterioration is defined as change from baseline that reaches a clinically meaningful deterioration threshold. The analysis will include all randomised participants, in the following populations: * TROP2 biomarker positive population * ITT population The measure of interest is the HR of time to deterioration in GHS/QoL. | Approximately 6 years |
Pharmacokinetics (PK) | Concentration of rilvegostomig, Dato-DXd, total anti TROP2 antibody, and MAAA 1181a (payload deruxtecan) in plasma or serum and PK parameters (peak and trough concentrations). | Approximately 6 years |
Immunogenicity | Presence of ADA for Dato-DXd and rilvegostomig (confirmatory results, titres and neutralising antibodies for confirmed positive samples). | Approximately 6 years |
Second Progression-Free Survival (PFS2). | PFS2 is defined as the time from randomisation to the earliest of the progression events (following the initial progression), subsequent to first subsequent therapy, or death. Progression event includes radiological (RECIST 1.1) or clinical disease progression. The date of second progression will be recorded by the investigator in the eCRF and defined according to local standard practice. The analyses will include all randomised participants, as randomised, regardless of whether the participant withdraws from subsequent therapy and regardless of missed visits, in the following populations: * TROP2 biomarker positive population * ITT population The measure of interest is the HR of PFS2. | Approximately 6 years |
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