Phase III, Open-label, First-line Study of Dato-DXd in Combination With Durvalumab and Carboplatin for Advanced NSCLC Without Actionable Genomic Alterations
Sponsor: AstraZeneca
ClinicalTrials ID:NCT05687266
This Phase III study evaluates the efficacy and safety of Dato-DXd with durvalumab and carboplatin versus pembrolizumab with platinum-based chemotherapy in adults with advanced NSCLC without actionable genomic alterations. Participants are randomized 1:1, with primary objectives focusing on Progression Free Survival and Overall Survival in TROP2 biomarker-positive patients.
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Program Overview
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).
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 Progression Free Survival (PFS) by BICR and Overall Survival (OS) in first-line treatment of TROP2 biomarker positive participants.
Eligibility Criteria
Inclusion:
- Participants ≥ 18 years at screening
- Histologically or cytologically documented NSCLC that at the time of randomisation is Stage IIIB or IIIC disease not amenable to surgical resection or definitive chemoradiation or Stage IV metastatic disease
- Lacks sensitising EGFR tumour tissue mutation and ALK and ROS1 rearrangements and has no documented tumour genomic alterations in NTRK, BRAF, RET, MET or other actionable driver oncogenes with approved and available therapies (actionable genomic alterations).
Testing is not required for tumors with squamous histology, with exceptions.
- ECOG PS of 0 or 1
- Archival tumour tissue
- Has adequate bone marrow reserve and organ function within 7 days before randomization
Exclusion:
- Mixed small-cell lung cancer and NSCLC histology; sarcomatoid variant of NSCLC
- History of another primary malignancy with exceptions
- Persistent toxicities caused by previous anti-cancer therapy not yet improved to Grade ≤ 1 or baseline, with exceptions.
- Spinal cord compression or clinically or radiologically active brain metastases
- History of leptomeningeal carcinomatosis.
- Known active or uncontrolled hepatitis B or C virus infection.
- Uncontrolled or suspected infection requiring IV antibiotics, antivirals, or antifungals.
- Clinically significant corneal disease
- History of non-infectious ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or has suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.
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