Phase III, Open-label, First-line Study of Dato-DXd in Combination With Durvalumab and Carboplatin for Advanced NSCLC Without Actionable Genomic Alterations
- Conditions
- NSCLC
- Interventions
- Registration Number
- NCT05687266
- Lead Sponsor
- AstraZeneca
- Brief Summary
This is a Phase III, randomized, open-label, multicenter, global study to compare the efficacy and safety of Datopotamab Deruxtecan (Dato-DXd) in combination with durvalumab and carboplatin compared with pembrolizumab in combination with histology-specific platinum-based chemotherapy as first-line treatment of adults with stage IIIB, IIIC, or IV NSCLC without actionable genomic alterations (including sensitizing EGFR mutations, and ALK and ROS1 rearrangements).
- Detailed Description
Participants with locally advanced or metastatic NSCLC without actionable tumor tissue genomic alterations and confirmed to meet all eligibility criteria will be randomized in a 1:1 ratio to Dato-DXd in combination with durvalumab and carboplatin versus pembrolizumab in combination with histology-specific platinum-based chemotherapy as first-line treatment.
The primary objectives of the study are to demonstrate superiority of Dato-DXd in combination with durvalumab and carboplatin relative to pembrolizumab in combination with platinum-based chemotherapy by assessment of the following:
1. PFS by BICR in first-line treatment of participants with non-squamous TROP2 biomarker positive locally-advanced or metastatic NSCLC
2. OS in first-line treatment of participants with non-squamous TROP2 biomarker positive locally-advanced or metastatic NSCLC
3. PFS by BICR in first-line treatment of participants with non-squamous locally-advanced or metastatic NSCLC
4. OS in first-line treatment of participants with non-squamous locally-advanced or metastatic NSCLC
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 1350
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Dato-DXd + Durvalumab + Carboplatin Datopotamab deruxtecan Participants will be randomized to receive 6.0mg/kg Dato-DXd plus 1120 mg durvalumab plus carboplatin area under the curve \[AUC\] 5 mg/mL/minute. Dato-DXd + Durvalumab + Carboplatin Durvalumab Participants will be randomized to receive 6.0mg/kg Dato-DXd plus 1120 mg durvalumab plus carboplatin area under the curve \[AUC\] 5 mg/mL/minute. Dato-DXd + Durvalumab + Carboplatin Carboplatin Participants will be randomized to receive 6.0mg/kg Dato-DXd plus 1120 mg durvalumab plus carboplatin area under the curve \[AUC\] 5 mg/mL/minute. Histologic-specific therapy Pembrolizumab Non-squamous NSCLC participants will be randomized to receive 200 mg pembrolizumab plus 500 mg/m2 pemetrexed plus either AUC 5 mg/mL/minute carboplatin or 75 mg/m2 cisplatin. Squamous NSCLC participants will be randomized to receive 200 mg of pembrolizumab plus 200 mg/m2 paclitaxel plus AUC 5 or 6 mg/mL/minute carboplatin. Histologic-specific therapy Paclitaxel Non-squamous NSCLC participants will be randomized to receive 200 mg pembrolizumab plus 500 mg/m2 pemetrexed plus either AUC 5 mg/mL/minute carboplatin or 75 mg/m2 cisplatin. Squamous NSCLC participants will be randomized to receive 200 mg of pembrolizumab plus 200 mg/m2 paclitaxel plus AUC 5 or 6 mg/mL/minute carboplatin. Histologic-specific therapy Carboplatin Non-squamous NSCLC participants will be randomized to receive 200 mg pembrolizumab plus 500 mg/m2 pemetrexed plus either AUC 5 mg/mL/minute carboplatin or 75 mg/m2 cisplatin. Squamous NSCLC participants will be randomized to receive 200 mg of pembrolizumab plus 200 mg/m2 paclitaxel plus AUC 5 or 6 mg/mL/minute carboplatin. Histologic-specific therapy Cisplatin Non-squamous NSCLC participants will be randomized to receive 200 mg pembrolizumab plus 500 mg/m2 pemetrexed plus either AUC 5 mg/mL/minute carboplatin or 75 mg/m2 cisplatin. Squamous NSCLC participants will be randomized to receive 200 mg of pembrolizumab plus 200 mg/m2 paclitaxel plus AUC 5 or 6 mg/mL/minute carboplatin. Histologic-specific therapy Pemetrexed Non-squamous NSCLC participants will be randomized to receive 200 mg pembrolizumab plus 500 mg/m2 pemetrexed plus either AUC 5 mg/mL/minute carboplatin or 75 mg/m2 cisplatin. Squamous NSCLC participants will be randomized to receive 200 mg of pembrolizumab plus 200 mg/m2 paclitaxel plus AUC 5 or 6 mg/mL/minute carboplatin.
- Primary Outcome Measures
Name Time Method Progression-Free Survival (PFS) by blinded independent central review (BICR) in the non-squamous TROP2 biomarker positive population Approximately 3 years PFS is defined as time from randomisation until progression per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1) as assessed by BICR, or death due to any cause.
Overall Survival (OS) in the non-squamous TROP2 biomarker positive population Approximately 4 years OS is defined as the time from randomisation until the date of death due to any cause.
PFS by BICR in the non-squamous population Approximately 3 years PFS is defined as time from randomisation until progression per RECIST 1.1 as assessed by BICR, or death due to any cause.
OS in the non-squamous population Approximately 4 years OS is defined as the time from randomisation until the date of death due to any cause.
- Secondary Outcome Measures
Name Time Method Clinical Outcome Assessments in ITT, non-squamous and TROP2 biomarker-defined populations Approximately 4 years Clinical Outcome Assessments, such as TTD in pulmonary symptoms (dyspnoea, cough and chest pain) as measured by the NSCLC-SAQ, and TTD in physical functioning as measured by PROMIS Physical Function short form 8c
PFS by investigator in ITT, non-squamous and TROP2 biomarker-defined populations Approximately 3 years PFS is defined as time from randomisation until progression per RECIST 1.1 as assessed by investigator clinical assessment, or death due to any cause.
PFS by BICR in ITT and TROP2 biomarker-defined populations Approximately 3 years PFS is defined as time from randomisation until progression per RECIST 1.1 as assessed by BICR, or death due to any cause.
OS in ITT and TROP2 biomarker-defined populations Approximately 4 years OS is defined as the time from randomisation until the date of death due to any cause.
Objective Response Rate (ORR) in ITT, non-squamous and TROP2 biomarker-defined populations Approximately 4 years ORR is defined as the proportion of participants who have a confirmed Complete Response (CR) or confirmed Partial Response (PR), as determined by BICR per RECIST 1.1.
Duration of Response (DoR) in ITT, non-squamous and TROP2 biomarker-defined populations Approximately 4 years 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 clinical assessment or death due to any cause.
Pharmacokinetics of Dato-DXd when combined with durvalumab and carboplatin. Approximately 4 years Concentration of Dato-DXd, total anti-TROP2 antibody, and DXd (payload deruxtecan) in plasma and pharmacokinetic (PK) parameters (such as peak and trough concentrations, as data allow; sparse sampling).
Anti-Drug Antibody (ADA) for Dato-DXd Approximately 4 years The immunogenicity of Dato-DXd when combined with durvalumab and carboplatin.
Time to Second Progression or Death (PFS2) in ITT, non-squamous and TROP2 biomarker-defined populations Approximately 4 years 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.
Trial Locations
- Locations (1)
Research Site
🇻🇳Ho Chi Minh, Vietnam