Metastatic Non Small Cell Lung Cancer
Conditions
Keywords
Metastatic Non Small Cell Lung Cancer, Advanced Non Small Cell Lung Cancer, Datopotamab Deruxtecan (Dato-DXd), Pembrolizumab, Pemetrexed, Tropion-Lung07
Brief summary
This study is designed to assess the efficacy and safety of datopotamab deruxtecan (Dato-DXd) in combination with pembrolizumab versus pembrolizumab in combination with pemetrexed and platinum chemotherapy in participants with no prior therapy for advanced or metastatic non-squamous non-small cell lung cancer (NSCLC).
Detailed description
The primary objectives of the study are Progression Free Survival (PFS) and Overall Survival (OS) as first line therapy in participants with programmed death-ligand 1 (PD-L1) TPS \<50% and advanced or metastatic NSCLC without actionable genomic alternations, as well as participants who are TROP2 NMR+ at baseline. TROP2 NMR will be retrospectively assessed. Eligible participants will be randomized in a 1:1:1 ratio to a) Dato-DXd plus pembrolizumab plus platinum; b) Dato-DXd plus pembrolizumab; or c) pembrolizumab plus pemetrexed plus platinum. Platinum therapy will be either carboplatin or cisplatin at investigator discretion. The study will be divided into three periods: Screening Period (including tissue screening), Treatment Period, and Follow-up Period.
Interventions
DRUGPemetrexed
Pemetrexed will be administered as an intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle.
DRUGCarboplatin
Carboplatin will be administered an intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle for up to 4 cycles.
DRUGCisplatin
Cisplatin will be administered an intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle for up to 4 cycles.
DRUGDatopotamab Deruxtecan
Dato-DXd will be administered as an intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle.
DRUGPembrolizumab
Pembrolizumab will be administered as an intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle.
Sponsors
Daiichi Sankyo
AstraZeneca
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Sign and date the Main ICF, prior to the start of any study- specific qualification procedures. Is willing and able to comply with scheduled visits, drug administration plan, laboratory tests, other study procedures, and study restrictions. 2. Adults ≥18 at the time the Main ICF is signed. (Follow local regulatory requirements if the legal age of adult voluntary consent for study participation is \>18 years old). 3. Has tumor with PD-L1 TPS \<50% as determined by PD-L1 IHC 22C3 pharmDx assay by central testing (minimum of 6 slides). PD-L1 expression results available at the same central laboratory from screening for the purpose of entry into another Dato-DXd study may be used for tissue screening purposes in this study as long as the subject has not been randomized/enrolled in the other study. 4. Has provided a formalin-fixed tumor tissue sample (minimum of 4 × 4-micron sections or block equivalent) for the measurement of TROP2 protein expression and for the assessment of other exploratory biomarkers. This tissue requirement is in addition to the tissue required for PD-L1 testing for tissue screening purposes. If a documented law or regulation prohibits (or does not approve) sample collection, then such sample will not be collected, and the subject is still eligible for the study. 5. Has not been treated with systemic anticancer therapy for advanced or metastatic non-squamous NSCLC. Subjects who received adjuvant or neoadjuvant therapy other than those listed in the
Exclusion criteria
are eligible if the adjuvant/ neoadjuvant therapy was completed at least 6 months prior to the diagnosis of advanced/metastatic disease and should not have progressed on or within the 6 months of completion. 6. Has measurable disease based on local imaging assessment using RECIST v1.1; radiographic tumor assessment must be performed within 28 days before randomization. Key
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival Based on Blinded Independent Central Review in All Randomized Participants | From randomization until disease progression or death (whichever occurs first), up to approximately 43 months | Progression-free Survival (PFS) is defined as the time from randomization to the first documented radiographic disease progression or death due to any cause, whichever occurs first, assessed by blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1. |
| Progression-free Survival Based on Blinded Independent Central Review in All Randomized Participants who are TROP2 NMR positive | From randomization until disease progression or death (whichever occurs first), up to approximately 43 months | Progression-free Survival (PFS) is defined as the time from randomization to the first documented radiographic disease progression or death due to any cause, whichever occurs first, assessed by blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1. |
| Overall Survival in All Randomized Participants | From randomization until disease progression or death (whichever occurs first), up to approximately 76 months | Overall Survival (OS) is defined as the time from randomization to death due to any cause. |
| Overall Survival in All Randomized Participants who are TROP2 NMR positive | From randomization until disease progression or death (whichever occurs first), up to approximately 76 months | Overall Survival (OS) is defined as the time from randomization to death due to any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate by Blinded Independent Central Review in All Randomized Participants | From randomization until disease progression or death (whichever occurs first), up to approximately 43 months | Objective Response Rate (ORR) is defined as the proportion of participants who achieved a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR), assessed by BICR per RECIST Version 1.1. |
| Objective Response Rate by Blinded Independent Central Review in All Randomized Participants who are TROP2 NMR positive | From randomization until disease progression or death (whichever occurs first), up to approximately 43 months | Objective Response Rate (ORR) is defined as the proportion of participants who achieved a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR), assessed by BICR per RECIST Version 1.1. |
| Progression-free Survival by Investigator in Both All Randomized Participants and Randomized Participants who are TROP2 NMR positive | From randomization until disease progression or death (whichever occurs first), up to approximately 43 months | Progression-free Survival (PFS) is defined as the time from randomization to the first documented radiographic disease progression or death due to any cause, whichever occurs first, assessed by the Investigator per RECIST Version 1.1. |
| Objective Response Rate by Investigator in Both All Randomized Participants and Randomized Participants who are TROP2 NMR positive | From randomization until disease progression or death (whichever occurs first), up to approximately 43 months | Objective Response Rate (ORR) is defined as the proportion of participants who achieved a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR), assessed by the Investigator per RECIST Version 1.1. |
| Duration of Response by BICR and Investigator in Both All Randomized Participants and Randomized Participants who are TROP2 NMR positive | From date of first objective response (CR or PR) to date of first radiographic disease progression or death due to any cause (whichever occurs first), up to approximately 43 months | Duration of Response (DoR) is defined as the time from the date of the first documentation of objective response (confirmed CR or confirmed PR) to the date of the first radiographic disease progression or death due to any cause, whichever occurs first, assessed by BICR and by the Investigator per RECIST Version 1.1. |
| Time to Response by BICR and Investigator in Both All Randomized Participants and Randomized Participants who are TROP2 NMR positive | From randomization to date of first objective response (CR or PR), up to approximately 43 months | Time to Response (TTR) is defined as the time from randomization to the date of the first documentation of objective response (confirmed CR or confirmed PR) in responding participants, assessed by BICR and by the Investigator per RECIST Version 1.1. |
| Disease Control Rate by BICR and Investigator in Both All Randomized Participants and Randomized Participants who are TROP2 NMR positive | From randomization until disease progression or death (whichever occurs first), up to approximately 43 months | Disease Control Rate (DCR) is defined as the proportion of participants who achieved a BOR of confirmed CR, confirmed PR, or stable disease (SD), assessed by BICR and by the Investigator per RECIST Version 1.1. |
| Progression-free Survival 2 in Both All Randomized Participants and Randomized Participants who are TROP2 NMR positive | From randomization until disease progression or death (whichever occurs first), up to approximately 76 months | Progression-free Survival 2 (PFS2) is defined as the time from randomization to the first documented radiographic disease progression or death due to any cause, whichever occurs first, assessed by local standard clinical practice |
| Time to Deterioration | From randomization until disease progression or death (whichever occurs first), up to approximately 76 months | Time to Deterioration (TTD) is defined as the time from randomization to first onset of a ≥10-point increase in cough, chest pain, or dyspnea, confirmed by a second adjacent ≥10-point increase from randomization in the same symptom, or confirmed by death within 21 days of a ≥10-point increase from randomization, assessed the European Organization for Research and Treatment of Cancer Lung cancer module (EORTC-QLQ-LC13). |
| Number of Participants With Treatment-emergent Adverse Events (TEAE) | Up to 76 months | A TEAE is defined as an AE with a start or worsening date on or after the start date of study treatment until 37 days after the end date of study treatment. |
| Proportion of Participants Who Are Anti-Drug Antibody (ADA)-Positive (Baseline and Post-Baseline) and Proportion of Participants Who Have Treatment-emergent ADA | Baseline and up to 76 months | The immunogenicity of Dato-DXd in combination with pembrolizumab will be assessed. |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, China, Czechia, France, Germany, Greece, Hong Kong, Hungary, Italy, Japan, Mexico, Netherlands, Poland, Portugal, Romania, South Korea, Spain, Switzerland, Taiwan, Thailand, Turkey (Türkiye), United Kingdom, United States
Contacts
STUDY_DIRECTORGlobal Clinical Leader
Daiichi Sankyo
Outcome results
None listed