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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
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.
Study details:
This is a global Phase III, open-label, randomised, multicentre study assessing the efficacy and safety of osimertinib in combination with Datopotamab Deruxtecan compared with osimertinib in participants with locally advanced or metastatic EGFRm (Ex19del and/or L858R) NSCLC who have not received any prior therapy for advanced disease.
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: 2024-04-29
Primary completion: 2028-03-21
Study completion finish: 2032-05-25
Study type
TREATMENT
Phase
PHASE3
Trial ID
NCT06350097
Intervention or treatment
DRUG: Osimertinib
DRUG: Datopotamab Deruxtecan
Conditions
- • Non-small Cell Lung Cancer
Find a site
Closest Location:
Research Site
Research sites nearby
Select from list below to view details:
Research Site
Clayton, Not Specified, Australia
Research Site
Kogarah, 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: Osimertinib in combination with Datopotamab Deruxtecan
| DRUG: Osimertinib
|
ACTIVE_COMPARATOR: Arm 2: Osimertinib monotherapy
| DRUG: Osimertinib
|
What is the study measuring?
Primary outcome
Primary Outcome Measure | Primary Outcome Description | Primary Outcome Time Frame |
---|---|---|
To demonstrate the superiority of osimertinib in combination with Datopotamab Deruxtecan relative to osimertinib by assessment of PFS by BICR in all randomised participants. | PFS is defined as time from randomisation until progression per RECIST 1.1 as assessed by BICR, or death due to any cause (in the absence of progression). | It is anticipated that it will be performed approximately 3 years after the first participant is randomised. |
Secondary outcome
Secondary Outcome Measure | Secondary Outcome Description | Secondary Outcome Time Frame |
---|---|---|
To demonstrate the superiority of osimertinib in combination with Datopotamab Deruxtecan relative to osimertinib by assessment of OS in all randomised participants. | OS defined as the time from randomisation until the date of death due to any cause. | It is anticipated that it will be performed approximately 7 years after the first participant has been randomised. |
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 | Central nervous system progression-free survival (CNS PFS) is defined as the time from randomisation until the date of objective CNS progression assessed by CNS BICR or death (by any cause in absence of CNS progression). | It is anticipated that it will be performed approximately 3 years after the first participant is randomised. |
To demonstrate the effectiveness of osimertinib in combination with Datopotamab Deruxtecan relative to osimertinib by assessment of PFS by investigator in all randomised participants. | PFS is defined as time from randomisation until progression per RECIST 1.1 as assessed by investigator, or death due to any cause (in the absence of progression). | It is anticipated that it will be performed approximately 3 years after the first participant is randomised. |
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. | ORR is defined as the proportion of participants who have a confirmed CR or confirmed PR, as determined by BICR (and investigator) per RECIST 1.1. | It is anticipated that it will be performed approximately 3 years after the first participant is randomised. |
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. | DoR is defined as the time from the date of first documented confirmed response until date of documented progression per RECIST 1.1, as assessed by BICR (and investigator) assessment or death due to any cause. The measure of interest is the median of DoR. | It is anticipated that it will be performed approximately 3 years after the first participant is randomised. |
To demonstrate the effectiveness of osimertinib in combination with Datopotamab Deruxtecan relative to osimertinib on the prevention of CNS metastases | Neuro-radiologist assessments according to CNS RECIST 1.1 to determine the presence/absence of CNS lesions at progression in participants without CNS metastases at baseline. | It is anticipated that it will be performed approximately 3 years after the first participant is randomised. |
To demonstrate the effectiveness of osimertinib in combination with Datopotamab Deruxtecan relative to osimertinib by assessment of PFS2 in all randomised participants | PFS2 will be defined as the time from randomisation to the earliest of the progression event (following the initial progression) subsequent to first subsequent anti-cancer therapy, or death. | It is anticipated that it will be performed approximately 7 years after the first participant has been randomised. |
To assess the PK of osimertinib and Datopotamab Deruxtecan | Concentration of osimertinib and its metabolite AZ5104, Datopotamab Deruxtecan, total anti-TROP2 antibody and DXd in plasma. | It is anticipated that it will be performed approximately 7 years after the first participant has been randomised. |
To investigate the immunogenicity of Datopotamab Deruxtecan | Presence of ADAs for Datopotamab Deruxtecan (confirmatory results: positive or negative, titres, and neutralizing antibodies). | It is anticipated that it will be performed approximately 7 years after the first participant has been randomised. |
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 | Concordance of EGFR mutation status between the local EGFR mutation test and the central cobas® EGFR Mutation Test v2 results from tumour samples with evaluable results. | It is anticipated that it will be performed approximately 3 years after the first participant is randomised. |
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 | PFS by Investigator by plasma EGFR mutation status PFS is defined as time from randomisation until progression per RECIST 1.1 as assessed by investigator, or death due to any cause (in the absence of progression). | It is anticipated that it will be performed approximately 7 years after the first participant has been randomised. |
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