Dato-DXd Plus Pembrolizumab as First-line Therapy in Advanced/Metastatic NSCLC: Phase 3 TROPION-Lung07 Trial Design

Although immunotherapy (IO) has improved survival in patients with advanced/metastatic non-small cell lung cancer (NSCLC), outcomes remain poor in patients with PD-L1 expression <50%. More effective treatments are needed. The global phase 3 TROPION-Lung07 trial will evaluate datopotamab deruxtecan (Dato-DXd) plus pembrolizumab with or without platinum chemotherapy (Pt-CT) as first-line therapy in patients with advanced/metastatic NSCLC without actionable genomic alterations and PD-L1 expression <50%. The trial’s design was discussed at the European Society for Medical Oncology (ESMO) Congress 2023.

To be eligible for inclusion, patients must have stage IIIB/C NSCLC that is ineligible for resection or definitive chemoradiation or stage IV disease and must not have received prior systemic therapy for advanced/metastatic NSCLC. Approximately 975 patients will be randomized 1:1 to Dato-DXd 6 mg/kg plus pembrolizumab 200 mg (max, 35 cycles) with or without Pt-CT (cisplatin 75 mg/m² or carboplatin area under the curve 5; max, 4 cycles) every 3 weeks or pemetrexed 500 mg/m² plus pembrolizumab 200 mg plus Pt-CT every 3 weeks.

The patients will be stratified by PD-L1 level, Eastern Cooperative Oncology Group (ECOG) performance status, geographic region, and investigator choice of Pt-CT. The primary end points of the trial are progression-free survival (PFS) and overall survival (OS), and secondary end points include objective response rate, duration of response, time to response, disease control rate, and safety. Patient-reported outcomes, pharmacokinetics, and biomarkers will also be explored. Enrollment is currently ongoing in the United States, Australia, China, Japan, the Republic of Korea, Taiwan, and Thailand. The clinical trial identification number is NCT05555732.

Source: Okamoto I. TROPION-Lung07: a phase III trial of datopotamab deruxtecan
(Dato-DXd) plus pembrolizumab (pembro) with or without platinum chemotherapy (Pt-CT) as first-line (1L) therapy in advanced/metastatic (adv/met) non-small cell lung cancer (NSCLC) with PD-L1 expression. Abstract of a poster presented at the ESMO Congress 2023; October 20-24, 2023; Madrid, Spain.