Datopotamab Deruxtecan Plus Pembrolizumab in Patients With Untreated Advanced/ Metastatic NSCLC

Among patients with advanced/metastatic non-small cell lung cancer (NSCLC), first-line immunotherapy significantly improves survival; the anti-PD-1 antibody pembrolizumab alone has shown superior efficacy over chemotherapy in untreated patients with advanced NSCLC and PD-L1 expression ³50%. However, most patients will eventually experience progression.

The phase 1 TROPION-PanTumor01 study showed that monotherapy with datopotamab deruxtecan (Dato-DXd), an antibody-drug conjugate composed of a humanized anti-TROP IgG1 monoclonal antibody covalently linked to a topoisomerase I inhibitor, demonstrated an objective response rate (ORR) of 28% and a tolerable safety profile in pretreated patients with NSCLC. Subsequently, the phase 1b trial evaluated Dato-DXd combined with pembrolizumab and showed a preliminary ORR of 62% and a disease control rate of 100%. The most frequent treatment-emergent adverse events were stomatitis and nausea.

The details of TROPION-Lung08, a phase 3, global, randomized, open-label, active-controlled trial, were presented at WCLC 2023 in Singapore. The trial is now enrolling approximately 740 patients to evaluate the efficacy and safety of Dato-DXd plus pembrolizumab versus pembrolizumab alone in treatment-naïve patients with advanced/metastatic NSCLC without actionable genomic alterations and PD-L1 expression ³50%. Patients will be randomized 1:1 to receive Dato-DXd 6 mg/kg plus pembrolizumab 200 mg or pembrolizumab 200 mg alone via infusion every 21 days until disease progression, discontinuation, or 35 cycles of pembrolizumab.

The primary end points of the study will include progression-free survival (PFS) and overall survival; secondary end points will include ORR, investigator-assessed PFS, PFS2, duration of response, time to response, disease control rate, time to deterioration, safety, and antidrug antibody prevalence. Pharmacokinetic parameters, biomarkers, and patient-reported outcomes will also be explored.

Source: Zhou C, Levy BP, Sands J, et al. TROPION-Lung08: Datopotamab deruxtecan plus pembrolizumab in untreated advanced/metastatic non-small cell lung cancer (NSCLC). Abstract of a poster presented at the 2023 World Conference on Lung Cancer; September 9-12, 2023; Singapore.