Metastatic Non-small Cell Lung Cancer
Conditions
Keywords
Epidermal growth factor receptor gene mutation, Standard of Care, Locally, advanced carcinoma, Metastatic carcinoma, Non-small cell lung cancer, Dato-dxd, Datopotamab deruxtecan, Osimertinib, Tagrisso, Pemetrexed, Carboplatin, Cisplatin
Brief summary
This study will assess the effect of Dato-DXd in combination with osimertinib or Dato-DXd monotherapy versus platinum-based doublet chemotherapy in terms of progression-free survival (PFS).
Detailed description
This is a Phase III, open-label, 3-arm, multicenter study assessing the effects of Dato-DXd in combination with osimertinib or Dato-DXd monotherapy versus platinum-based doublet chemotherapy in participants with epidermal growth factor receptor gene mutation (EGFRm) locally advanced or metastatic non-small cell lung cancer (NSCLC) whose disease has progressed on prior osimertinib treatment. Participants will be randomized in a 1:1:1 ratio to one of the following intervention groups: 1. Dato-DXd + osimertinib combination therapy 2. Dato-DXd monotherapy 3. Platinum-based doublet chemotherapy Participants will receive study intervention until Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) -defined radiological progression by the investigator, unacceptable toxicity, or other discontinuation criterion is met. After study intervention discontinuation, all participants will undergo an end of treatment (EoT) visit within 35 days of discontinuation and will be followed up for safety assessments 28 (+ 7) days after their last dose of study intervention.
Interventions
DRUGDato-DXd
Dato-DXd will be administered as IV infusion.
DRUGOsimertinib
Osimertinib will be administered orally.
DRUGPemetrexed
Pemetrexed will be administered as IV infusion.
DRUGCarboplatin
Carboplatin will be administered as IV infusion.
DRUGCisplatin
Cisplatin will be administered as IV infusion.
Sponsors
AstraZeneca
Daiichi Sankyo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 130 Years
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed non-squamous NSCLC. * Must have evidence of documented pre-existing EGFRm information (EGFRm known to be associated with (epidermal growth factor receptor \[EGFR\] tyrosine kinase inhibitor \[TKis\] sensitivity \[Ex19del, L858R, G719X, S768I, or L861Q\], either alone or in combination with other EGFR mutations, which may include T790M). * Documented extra-cranial radiologic progression on prior osimertinib monotherapy (as most recent line of treatment) in the adjuvant, locally advanced, or metastatic setting. * Less than or equal to (\<=2) prior lines of EGFR TKIs (osimertinib is the only permitted prior third generation EGFR TKI). * At least one lesion, not previously irradiated, that qualifies as a RECIST v1.1 TL at baseline and can be accurately measured at baseline. * World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Adequate bone marrow reserve and organ function within 7 days before randomization.
Exclusion criteria
* Use of chemotherapy, vascular endothelial growth factor inhibitor, immunotherapy or any anti-cancer therapy in the metastatic setting. Platinum-based chemotherapy in non-metastatic setting within 12 months prior to randomization. * History of another primary malignancy except for malignancy treated with curative intent with no known active disease within 2 years before the first dose of study intervention. * Any evidence of severe or uncontrolled systemic diseases, including, but not limited to active bleeding diseases, active infection, active ILD/pneumonitis, cardiac disease. * Has significant third-space fluid retention (example \[eg.\], ascites or pleural effusion) as judged by the investigator and is not amenable for required repeated drainage. * History of non-infectious ILD/pneumonitis including radiation pneumonitis that required steroids or drug-induced ILD, has current ILD/pneumonitis, or has suspected ILD/pneumonitis that cannot be ruled out by imaging at screening. * Has severe pulmonary function compromise resulting from intercurrent pulmonary illnesses. * Unstable spinal cord compression and/or unstable brain metastases. * Participants with symptomatic brain metastases (including leptomeningeal involvement). * Clinically significant corneal disease. * Uncontrolled infection requiring systemic antibiotics, antivirals, or antifungals, suspected infections or inability to rule out infections. Use of systemic antibiotics within 14 days of randomization. * Has known human immunodeficiency virus (HIV) infection that is not well controlled.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression free Survival (PFS) | Up to 2.5 years | PFS is defined as the time from randomization to Blinded Independent Central Review (BICR)-assessed progression using RECIST v1.1 or death due to any cause, regardless of whether the participant withdraws from study therapy, receives other anti-cancer therapy, or clinical progression. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Up to 3.5 years | OS is defined as time from randomization until the date of death due to any cause. |
| Central Nervous System Progression-free Survival (CNS PFS) | Up to 2.5 years | CNS PFS is defined as the time from randomization to BICR confirmed progression in the CNS or death due to any cause, regardless of whether the participant withdraws from study therapy, receives other anti-cancer therapy, or clinically progresses prior to BICR confirmed CNS modified RECIST v1.1 progression. |
| Objective Response Rate (ORR) | Up to 2.5 years | ORR is defined as the percentage of participants who have a confirmed complete response (CR) or confirmed partial response (PR), as determined by BICR per RECIST v1.1. |
| Duration of Response (DoR) | Up to 2.5 years | DoR is defined as the time from the date of first documented response until date of documented progression per RECIST v1.1, as assessed by BICR or death due to any cause. |
| Progression-free Survival-2 (PFS-2) | Up to 3.5 years | PFS2 is defined as the time from randomization to the earliest of the progression event (following the initial investigator assessed progression), after first subsequent therapy, or death. |
| Objective Response Rate (ORR) Using CNS Modified RECIST v1.1 | Up to 2.5 years | ORR is defined as the percentage of participants who have a confirmed CR or confirmed PR, using CNS modified RECIST v1.1. |
| Duration of Response (DoR) Using CNS Modified RECIST v1.1 | Up to 2.5 years | DoR is defined as the time from the date of first documented response until date of documented progression or death due to any cause using CNS modified RECIST v1.1. |
| Time to Deterioration in Pulmonary Symptoms | Up to 3.5 years | Time to deterioration (in pulmonary symptoms \[dyspnea, cough, and chest pain\]) is defined as the time from randomization until the date of deterioration. Deterioration is defined as change from baseline that reaches a meaningful change threshold. |
| Time to Deterioration in Physical Functioning | Up to 3.5 years | Time to deterioration in physical functioning as measured by Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function short form 8c will be evaluated. Time to deterioration (in physical functionating) is defined as the time from randomization until the date of deterioration. Deterioration is defined as change from baseline that reaches a meaningful change threshold. |
| Time to Deterioration in Global Health Status (GHS)/Quality of Life (QoL) | Up to 3.5 years | Time to deterioration in GHS/QoL as measured by the GHS/QoL scale from EORTC IL172 will be reported. Time to deterioration (in GHS/QoL) is defined as the time from randomization until the date of deterioration. Deterioration is defined as change from baseline that reaches a meaningful change threshold. |
| Pharmacokinetics (PK) of Dato-DXd | Up to 3.5 years | Concentration of Dato-DXd, total anti-TROP2 antibody and DXd in plasma. |
| Immunogenicity of Dato-DXd | Up to 3.5 years | Presence of antidrug antibody (ADAs) for Dato-DXd (confirmatory results: positive or negative, titers). |
Countries
Australia, Belgium, Brazil, Canada, China, France, Germany, Greece, Hong Kong, India, Israel, Italy, Japan, Malaysia, Netherlands, Philippines, Poland, Portugal, Romania, Singapore, South Korea, Spain, Taiwan, Thailand, United Kingdom, United States, Vietnam
Contacts
CONTACTAstraZeneca Clinical Study Information Center
Outcome results
None listed